APLAR 2016 Oral Abstracts

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Ankylosing Spondylitis APL16-0572 Baseline Results of Chinese Sub-population from PROOF A 5-year Observational Study of Long-term Disease Outcome in Axial Spondyloarthritis F. Huang 1 , C. Bao 2 , Y. Fang 3 , L. Wu 4 , L. Jiang 5 , D. He 6 , J. Xu 7 , F. Zhang 8 , X. Zhang 9 , L. Bi 10 , D. Poddubnyy 11 , M. Hojnik 12 1 Chinese PLA General Hospital, Rheumatology, Beijing, China 2 Renji Hospital of Shanghai Jiao Tong University School of Medicine, Rheumatology, Shanghai, China 3 Southwest Hospital- Third Military Medical University, Rheumatology, Chongqing, China 4 People's Hospital of Xinjiang Uygur Autonomous Region, Rheumatology, Urumqi, China 5 Zhongshan Hospital affiliated to Fudan University, Rheumatology, Shanghai, China 6 Guanghua Integrative Medicine Hospital, Rheumatology, Shanghai, China 7 First Affiliated Hospital of Anhui Medical University, Rheumatology, Hefei, China 8 Peking Union Medical College Hospital, Rheumatology and Clinical Immunology, Beijing, China 9 Guangdong General Hospital and Guangdong Academy of Medical Sciences, Rheumatology, Guangzhou, China 10 China-Japan Union Hospital of Jilin University, Rheumatology and Immunology, Changchun, China 11 Charité Universitätsmedizin Berlin, Rheumatology, Berlin, China 12 AbbVie, Global Medical Affairs Rheumatology, Ljubljana, Slovenia Objective: To report the baseline data of Chinese patients in PROOF, an ongoing multi-country study evaluating long-term outcomes in axSpA patients. Methods: PROOF is a prospective observational study evaluating axSpA patients (ASAS classification criteria and diagnosed ≤12 months before enrollment) in clinical practice over 5 years. Yearly assessments of disease activity (BASDAI, ASDAS-CRP), physical function (BASFI), quality-of- life (SF-12v2), productivity (WPAI-SHP), and pelvic X-ray (graded by local and central readers according to NY criteria) are performed. Results: 464 Chinese patients have been enrolled in PROOF [AS:307 (66%), nraxSpA:157 (34%); per investigator]. 84% fulfilled the imaging criterion (MRI:30.2%, X-ray:61.4%, Both:8.4%); 16% fulfilled the clinical arm. Comparison of demographic and clinical characteristics between AS and nr- axSpA patients in Chinese and overall population are shown (Table). A greater proportion of Chinese patients had AS subdiagnosis and differences in disease activity, physical function, and quality-of-life measures were observed between the Chinese and overall population. Baseline x-rays were captured for 403 (87%) patients; presently, both readers have scored x-rays of 368 patients (91% of available). 87.5% of patients retained their AS or nr-axSpA classification after the central reading. Substantial agreement on x-ray grading was observed between local and central readers: kappa=0.65 (95% CI, 0.560.74). Conclusions: PROOF aims to assess long-term outcomes of axSpA in clinical practice. Similar to the overall population, baseline results of the Chinese subpopulation confirmed comparable clinical features and disease burden between AS and nr-axSpA, highlighted a long referral delay, and showed good agreement between x-ray grading by local and central readers.

Transcript of APLAR 2016 Oral Abstracts

Page 1: APLAR 2016 Oral Abstracts

Ankylosing Spondylitis

APL16-0572 Baseline Results of Chinese Sub-population from PROOF – A 5-year Observational Study of Long-term Disease Outcome in Axial Spondyloarthritis F. Huang1, C. Bao2, Y. Fang3, L. Wu4, L. Jiang5, D. He6, J. Xu7, F. Zhang8, X. Zhang9, L. Bi10, D. Poddubnyy11, M. Hojnik12 1Chinese PLA General Hospital, Rheumatology, Beijing, China 2Renji Hospital of Shanghai Jiao Tong University School of Medicine, Rheumatology, Shanghai, China 3Southwest Hospital- Third Military Medical University, Rheumatology, Chongqing, China 4People's Hospital of Xinjiang Uygur Autonomous Region, Rheumatology, Urumqi, China 5Zhongshan Hospital affiliated to Fudan University, Rheumatology, Shanghai, China 6Guanghua Integrative Medicine Hospital, Rheumatology, Shanghai, China 7First Affiliated Hospital of Anhui Medical University, Rheumatology, Hefei, China 8Peking Union Medical College Hospital, Rheumatology and Clinical Immunology, Beijing, China 9Guangdong General Hospital and Guangdong Academy of Medical Sciences, Rheumatology, Guangzhou, China 10China-Japan Union Hospital of Jilin University, Rheumatology and Immunology, Changchun, China 11Charité Universitätsmedizin Berlin, Rheumatology, Berlin, China 12AbbVie, Global Medical Affairs Rheumatology, Ljubljana, Slovenia

Objective: To report the baseline data of Chinese patients in PROOF, an ongoing multi-country study evaluating long-term outcomes in axSpA patients.

Methods: PROOF is a prospective observational study evaluating axSpA patients (ASAS classification criteria and diagnosed ≤12 months before enrollment) in clinical practice over 5 years. Yearly assessments of disease activity (BASDAI, ASDAS-CRP), physical function (BASFI), quality-of-life (SF-12v2), productivity (WPAI-SHP), and pelvic X-ray (graded by local and central readers according to NY criteria) are performed.

Results: 464 Chinese patients have been enrolled in PROOF [AS:307 (66%), nraxSpA:157 (34%); per investigator]. 84% fulfilled the imaging criterion (MRI:30.2%, X-ray:61.4%, Both:8.4%); 16% fulfilled the clinical arm. Comparison of demographic and clinical characteristics between AS and nr-axSpA patients in Chinese and overall population are shown (Table). A greater proportion of Chinese patients had AS subdiagnosis and differences in disease activity, physical function, and quality-of-life measures were observed between the Chinese and overall population. Baseline x-rays were captured for 403 (87%) patients; presently, both readers have scored x-rays of 368 patients (91% of available). 87.5% of patients retained their AS or nr-axSpA classification after the central reading. Substantial agreement on x-ray grading was observed between local and central readers: kappa=0.65 (95% CI, 0.56–0.74).

Conclusions: PROOF aims to assess long-term outcomes of axSpA in clinical practice. Similar to the overall population, baseline results of the Chinese subpopulation confirmed comparable clinical features and disease burden between AS and nr-axSpA, highlighted a long referral delay, and showed good agreement between x-ray grading by local and central readers.

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Rheumatic Diseases – Basic Science APL16-0222 The therapeutic effects of mesenchymal stem cells on systemic lupus erythematosus is associated with NK cells Y. Hu1, R. Feng2, C. Liu1, B. Shi2, J. Qi2, J. Fan2, Z. Zhang2, Y. Wang1, W. Chen2, X. Tang2, G. Yao2, L. Sun1 1Drum Tower Clinical Medical College of Nanjing Medical University, Department of Rheumatology and Immunology, Nanjing, China 2The Affiliated Drum Tower Hospital of Nanjing University Medical School, Department of Rheumatology and Immunology, Nanjing, China

Although umbilical cord (UC)-derived mesenchymal stem cells (MSC) have been confirmed to exert therapeutic effects on systemic lupus erythematosus (SLE), the mechanism of UCMSC on SLE remains to be elucidated. Besides T and B cells, natural killer (NK) cells may have a role. Here, we explored the number and function of NK cells in SLE patients and in B6.MRL-Faslpr mice before and after the treatment of UCMSC. Compared with controls, NK cell percentages among lymphocytes were decreased in SLE patients and showed a positive correlation with anti-double-stranded DNA (anti-dsDNA) antibody. Functional experiments revealed a reduced degranulation of NK cell response to K562 target cells both at diagnosis and during conventional therapy in SLE patients. Consistent with the results in human, relative numbers of NK1.1+ cells were reduced in B6.MRL-Faslpr mice. Moreover, the decreased murine splenic NK cells were positively related to regulatory T cells, while negatively correlated with B cells and TH17 cells. UCMSC-treated group downregulated the serum IFN-γ, IL-2 and IL-10 in B6.MRL-Faslpr mice, which was correlated with the recovered NK cells. We conclude that SLE is associated with quantitative and functional defects in NK cells, which can be restored after the treatment of UCMSC. Further researches are needed to identify the mechanism of NK cell deficiency in SLE and to develop novel strategies targeting NK cells for immunotherapy.

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Genetics

APL16-0136 Two CAPS-like children caused by NLRP12 gene mutations W. Wang1, M. Wei1, L. Zhang1, L. Zhong1, H. Song1 1Peking Union Medical College Hospital - Chinese Academy of Medical Sciences, Pediatrics, Beijing, China

Objectives: Cryopyrin-associated periodic syndrome (CAPS) is an autosomal-dominant inherited disease, most were caused by NLRP3 mutation. General symptoms of CAPS are fatigue and fever. Local manifestations affect multiple tissues such as skin, joints, muscles, eyes, and the central nervous system. NLRP12 mutations was found in some CAPS-like patients since 2007. To our knowledge, there was no CAPS caused by NLRP12 mutation reported in Chinese mainland. The objective of the study is to make definite diagnosis of two CAPS-like children by gene analysis.

Methods: We detected NLRP3 gene of two unrelated cases of CAPS-like children and their parents by Sanger sequencing. If no suspicious pathogenic mutation was found, we detected their DNA by gene trapping high-throughput sequencing with an AIDs panel. After biological information analysis, we detected the suspicious pathogenic mutations of the family by Sanger sequencing to make diagnosis.

Results: (1)Both of the two cases had no mutation of NLRP3.(2)After high-throughput sequencing, both of the two cases found a mutation in NLRP12 (NM_001277126). A de novo mutation

c.1673T>G,p.L558R was found in case 1. A reported splicing mutation c.2072+2dupT was found in

Case 2 and her father.

Conclusions: (1) Two cases CAPS-like patients were caused by NLRP12 gene mutations. As far as we know, they were first reported in Chinese mainland. (2) For those patients with similar clinical manifestation to CAPS, We could detect both NLRP3 and NLRP12. Gene trap high-throughput sequencing is an effective and time-saving method.

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Gout

APL16-0239 Altered functional polarization of macrophages in different gouty models L. Liu1, X. Yu1, Z. Hejian1 1Hushan Hospital- Fudan University, Department of Rheumatology, Shanghai, China

Objectives: There are increasing evidences indicating that macrophages play a pivotal role in acute gouty inflammation. In this study, we assessed distinguished polarization states of macrophages in initiation, progression and resolution of acute gouty attack.

Methods: MSU crystal induced inflammation of rat ankles and mouse peritoneal cavities were established as in vivo models, while mouse peritoneal macrophages cultured and stimulated with MSU were considered as an in vitro model. Polarization states of macrophages in different time points form initiation to resolution of the inflammation were detected mainly by immunohistochemistry, immunofluorescence and flow cytometry.

Results: Infiltration of M1 was positively related with the severity of arthritis while M2 appeared in an early stage (Figure 1). Monocytes/macrophages in mouse peritoneal cavities which were thought to be recruited from circulation showed low expression of surface markers of both M1 and M2 during the MSU induced inflammation. Ratio of M1 was reduced from 94.3% to 6.76% gradually in the in vitro model, which was closely correlated with the concentrations of inflammatory chemokines released (Figure 2a). However, ratio of M2 was similarly reduced from 9.6% to 0.97% in this model (Figure 2b).

Conclusion: M1 was positively related with the severity of gouty arthritis. M2 appeared in an early stage, which, we speculate, might generate directly from M0 instead of M1. Further analysis into how M0 directly polarized to M2 has the potential to identify a new modulatory role for M0 in acute gouty inflammation.

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APL16-0497 Synovial fluid uric acid level: A simple diagnostic tool for diagnosis of gout B. Vaidya1 1National Center for Rheumatic Diseases, Rheumatology, Kathmandu, Nepal

Background and aims: Examination of urate crystal in synovial fluid remains the gold standard for diagnosis of gout. The technology is not universally available. Synovial fluid uric acid level can be easily measured by biochemistry analyser. We aim to study the utility synovial fluid to serum uric acid ratio for the diagnosis of gout.

Methods: A cross sectional study conducted at rheumatology out-patient clinic of National Center of Rheumatic Diseases (NCRD). Patients presenting with acute gout clinically and with synovial effusion of other causes were included in the study. Synovial fluid aspiration was done in all patients and fluid was sent of assessment of uric acid level, pH and cell counts. Simultaneous serum samples were sent for uric acid levels. The ratio of synovial fluid to serum uric acid level (SSR) was calculated for each patient. ROC curve was plotted to calculate the cutoff value of SSR ratio for the diagnosis of gout. Internal validation was done using bootstrapping. Difference in SSR ratio between gout and non-gout effusion was calculated using the t-test.

Results: A total of 91 patients presenting synovial effusion were studied. Diagnostic criteria for gout were fulfilled by 40. Rest of the patients included cases of osteoarthritis and pseudogout. A SSR if ≥ 1.10 had a sensitivity of 64% and specificity of 80% for the diagnosis of gout.

Conclusion: Synovial fluid to serum urate concentration can be used as a diagnostic tool for gout when polarizing microscope for crystal examination is not available.

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APL16-0737 Ultrasonographic determination of the prevalence and risk factors for renal and bladder calculi formation in patients with gout M. Tee1, C. Lustre2, I.E. Afos1, J.P. Cañal2 1Philippine General Hospital, Medicine, Metro Manila, Philippines 2Philippine General Hospital, Radiology, Metro Manila, Philippines

We assessed the prevalence and risk factors for renal and bladder calculi formation among gout patients through a prospective descriptive study. We did kidney and urinary bladder ultrasonography on 80 patients, aged 59 ± 12 years old, using a Siemens Sonoline G40 machine. Calculi size, number and location/s were recorded, categorized into: calyces, pelvis, proximal ureter, medulla or parenchyma. The images were reviewed in blinded retrospective manner by another radiologist.

We found that 42.5% of patients with gout have renal calculi on ultrasonography. Majority (70%) of the calculi measured less than 1 cm with an average size of 0.81 ± 0.48 cm. Forty seven percent (47%, 16/34) of patients with chronic tophaceous gout had calculi while 39% (18/46) of those without tophi had calculi (p=.478). Looking at the calculi as a focal point, 47%, (16/34) of those with renal calculi had tophi. Ultrasound evidence of chronic kidney disease was appreciated in 14.5% (5/34) of patients with renal calculi. Limitations of ultrasonographic studies include: 1) inability to distinguish between arcuate artery calcifications from parenchymal calculi; and 2) distal obstruction by a calculus. The correlation of renal calculi formation in gout patients with some identified risk factors are currently being investigated in a larger study.

Our study revealed that renal calculi in Filipino patients with gout is two-fold more prevalent than previously reported. Thus, renal ultrasonography should be part of the management of these patients in order to intervene with effective medical and/or surgical methods as early as possible.

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APL16-0783 Indirect comparison of urate-lowering therapies for hyperuricemic patients with or without gout: meta-analysis of randomized, controlled trials M. Fan1, J. Liu2, B. Zhao3, X. Wu1, J. Gu1 1The Third Affiliated Hospital of Sun Yat-Sen University, Rheumatology, Guangzhou, China 2The First Affiliated Hospital of Sun Yat-Sen University, cardiology, Guangzhou, China 3The First Affiliated Hospital of Sun Yat-Sen University, Anesthesiology, Guangzhou, China

Objective: To assess the urate-lowering efficacy and safety of febuxostat, allopurinol and benzbromarone in hyperuricemic patients with or without gout.

Methods: We included all the randomized controlled trials (RCTs) that compared any urate-lowering medication with placebo or head to head. The efficacy outcomes included the proportions of achieving the target urate level (< 6.0 mg/dl) at final visit or last 3 visits and the percentage of gout flares during the first 8 weeks. The safety outcomes included total adverse events (AEs), withdrawals due to AEs and serious AEs. A Bayesian network model was used to compare all interventions simultaneously.

Results: Sixteen RCTs (6645 patients) were included in the analysis. All urate-lowering therapies were more likely to achieve the target urate level at final visit and last 3 visits than placebo, but had an inconclusive higher risk of gout flares (table 1). Furthermore, all of the febuxostat doses (40, 80, 120, 240 mg/day) had a higher proportion of achieving the target urate level at final visit than allopurinol. With febuxostat dosages increased, more patients achieved the target urate level. Febuxostat 240 mg/day was the most effective drug for serum urate normalization. Regarding safety, there were no significant differences among urate-lowering therapies and placebo for total AEs, withdrawals due to AEs and serious AEs, except that allopurinol had a higher risk of total AEs than febuxostat 120mg/day.

Conclusions: Compared to placebo, all urate-lowering therapies are effective in achieving target urate level for hyperuricemic patients. Febuxostat is more efficacious than allopurinol for serum urate normalization.

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Human Autoimmune Disease Genetics

APL16-0262 eQTLs of IL12A were associated with primary biliary cirrhosis in Chinese Han P. Li1, G. Lu1, Z. Wu1, S. Chen1, J. Li1, X. Wen1, H. Zhang1, F. Zhang1, Y. Li1 1Peking Union Medical College Hospital, Rheumatology and Clinical Immunology, Beijing, China

GWAS in Europeans have revealed that IL12A was strongly associated with PBC. However, this association was not detected in replication studies conducted in Chinese Han and Japanese populations.

In order to verify whether the genetic variants of IL12A contributed to the pathogenesis of PBC in Chinese, a replication study with 22 SNPs around IL12A was performedin a cohort of 586 PBC cases and 726 healthy controls. The top two most significant association signal was detected for rs4679868 (p=6.59E-05, OR=1.554 [1.253-1.927]) and rs6441286 (p=8.00E-05, OR=1.551[1.250-1.924]). These two SNPs were strongly linked with each other (r2 = 0.981), and both of them had been found to be significantly associated with PBC in European populations. An expression Quantitative Trait Loci (eQTL) analysis was carried out based on the observation that these two SNPs were located in proximity to two enhancers verified by luciferase reporter systems in HEK293 cell line. Conducted using the publically accessible data, the result of eQTL analysis showed that the risk alleles of rs4679868 and rs6441286 were significantly associated with the decreased expression of IL12A in the lymphoblastoid cell lines of Chinese Han (p = 0.0031 for rs4679868, and p = 0.0073 for rs6441286, respectively). However, the risk alleles of the two SNPs were significantly associated with the down-regulation of SCHIP1, a celiac disease susceptible gene 91.5Kb upstream of IL12A.

These results not only demonstrated that IL12A was associated with PBC in Chinese Han population, but also showed the potential mechanism of its involvement in pathogenesis of PBC.

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APL16-0485 Genetic landscape of interactive effects of HLA-DRB1 alleles on susceptibility to rheumatoid arthritis in the Japanese population. C. Terao1, K. Ohmura2, K. Ikari3, A. Taniguchi3, S. Momohara3, H. Yamanaka3, T. Mimori2, F. Matsuda4 1Brigham and Women’s Hospital, Divisions of Genetics and Rheumatology- Department of Medicine, Boston, USA 2Kyoto University Graduate School of Medicine, Department of Rheumatology and Clinical Immunology, Kyoto, Japan 3Tokyo Women's Medical University, Institute of Rheumatology, Tokyo, Japan 4Kyoto University Graduate School of Medicine, Center for Genomic Medicine, Kyoto, Japan

Background: HLA-DRB1 is the strongest susceptibility gene to rheumatoid arthritis (RA) beyond population. Recent study in the European population showed that HLA-DRB1 alleles showed significant interactive effects on susceptibility to RA with anti-citrullinated peptide antibody (ACPA). However, due to difference in allelic distribution, genetic landscape of HLA-DRB1 interactive effects on RA susceptibility might be different between populations.

Objective: to evaluate interactive effects of HLA-DRB1 alleles on RA susceptibility in the Japanese population

Methods: A total of 3,062 ACPA(+) cases and 2,005 controls were used for the analyses of RA susceptibility. Both allelic non-additive effects and interactive effects of allelic combinations were analyzed in logistic model. The significant levels were set by Bonferroni’s correction.

Results: We obtained evidence of non-additive effects on RA susceptibility for HLA-DRB1*04:05, the most common susceptibility allele to RA in the Japanese population, and *08:03 (p=0.00023 and 3.6x10-5, respectively). HLA-DRB1*04:01, the most common susceptibility allele to RA in the European population, 01:01 and 15:01, showing significant non-additive effects in European population, did not show significant results. The combination of DRB1*04:05 and *08:03 showed the most significant interactive effect on RA susceptibility (p=4.3x10-4) which was not reported by the previous European study. The combination of DRB*04:05 and *09:01, a combination previously reported in Korean studies, did not demonstrate a significant result.

Conclusions: HLA-DRB1*04:05 and *08:03 showed non-additive effects and an interactive effect with each other on RA susceptibility in the Japanese population. The allelic non-additive effects on RA susceptibility might vary between populations and depend on allelic distribution.

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Miscellaneous

APL16-1343 Association of large intergenic noncoding RNA expression with disease activity and organ damage in systemic lupus erythematosus W. Yanfang1, T. Yuanjia2, S. Nan2 1Fujian Provincial Hospital, Department of Rheumatology, Fujian Province, China 2Ren Ji Hospital- School of Medicine- Shanghai Jiao Tong University, Department of Rheumatology, Shanghai, China

Introduction: While there is growing evidence that large intergenic noncoding RNAs (lincRNAs) can regulate gene expression and widely take part in normal physiological and disease conditions, our knowledge of SLE-related lincRNAs remains limited. The study was aimed to detect the levels of four lincRNAs (ENST00000500949: linc0949, ENST00000500597: linc0597, ENST00000501992: linc1992 and ENST00000523995: linc3995) which were involved in innate immunity, in the peripheral blood mononuclear cells (PBMC) of systemic lupus erythematosus (SLE) patients and correlate these lincRNA levels with disease activity, organ damage, clinical features and medical therapies.

Methods: PBMC were obtained from 102 SLE patients, 54 rheumatoid arthritis (RA) patients and 76 healthy donors. LincRNAs expression levels were measured by real time quantitative polymerase chain reaction (RT-qPCR). Disease activity was assessed using the SLE Disease Activity Index 2000 scores (SLEDAI-2K), and organ damage was evaluated with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI).

Results: Linc0949 and linc0597 were significantly decreased in SLE patients compared with RA patients and normal controls. Linc0949 was correlated with SLEDAI-2K (r=-0.329, P=0.0007), as well as with C3 levels (r=0.348, P=0.0003). The level of linc0949 was also reduced in SLE patients with the presence of cumulative organ damage. In addition, the descending expression of linc0949 was associated with lupus nephritis. Linc0949 expression significantly increased after treatment. While neither disease activity nor organ damage correlated with linc0597 expression.

Conclusion: Our result provided novel empirical evidence that linc0949 could be one of potential biomarkers for diagnosis, disease activity and therapeutic response in SLE disease.

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Myositis

APL16-0445 Clinical Association of Chemokine (C-X-C motif) Ligand 1 (CXCL1) with Interstitial Pneumonia with Autoimmune Features (IPAF) M. Liang1, Z. Jiang2, H. Zou2 1Huashan Hospital, Division of Rheumatology, Shanghai, China 2Institute of Rheumatology- Immunology and Allergy- Fudan University- Shanghai 200040- PR China., Division of Rheumatology- Huashan Hospital- Fudan University- Shanghai 200040- PR China., Shanghai, China

Interstitial pneumonia with autoimmune features (IPAF) has been recently proposed to describe interstitial lung disease (ILD) in patients with an underlying autoimmune process that does not meet established criteria for a connective tissue disease (CTD). In this study, we investigated the clinical characteristics of IPAF and compared them with idiopathic interstitial pneumonia (IIP), meanwhile, we evaluated the clinical implications of CXCL1-CXCR2 axis in IPAF.

Our results suggested that middle-age onset, an equal ratio of male to female patients, decreased DLCO, and increased ESR were typical characteristics of IPAF. Furthermore, a multiplex bead-based immunoassay demonstrated the increased plasma levels of CXCL1, IL-4, IL-13, IL-6 and IL-17 in IPAF compared to IIP, COPD and healthy controls. In addition, the plasma concentration of CXCL1 was clinically associated with DLCO, ESR level, and the involved parenchyma extension (determined by FibMax) in IPAF patients. Furthermore, circulating CXCL1 levels were the highest in the IPAF patients with acute exacerbations. Nevertheless, no such close association of the levels of IL-4, IL-13, IL-6 and IL-17 with those clinical parameters was found. CXCR2, the chemokine receptor for CXCL1, was readily observed in the loosely formed lymphoid aggregates in IPAF lungs but was considerably lower in IIP lungs and rare in normal lungs. Interestingly, the increased CXCL1 concentration in BALF paralleled the neutrophil counts in IPAF BALF.

Overall, the plasma concentration of CXCL1 indicated the degree of disease activity and the prognosis in patients with IPAF. Thus, the CXCL1/CXCR2 axis appears to be involved in the progression of IPAF.

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APL16-0529 Pregnancy in polymyositis/dermatomyositis: retrospective results from a tertiary center in China Z. Zhi Qiang1, L. Fu An2, Y. Jing1, Z. Feng Chun1, Z. Xiao Feng1, Y. Xin1 1Peking Union Medical College Hospital, Rheumatology, BEIJING, China 2Zhangzhou Municipal Hospital, Rheumatology, Zhang Zhou-Fujian Province- China, China

Objectives: To examine if patients with polymyositis/dermatomyositis are at higher risk of complicated pregnancies.

Methods: A retrospective cohort in a large tertiary center of North China, evaluated the outcomes of 144 pregnancies in 62 women with polymyositis/dermatomyositis. Generalized mixed effect logistic models were fitted to assess the effect of occurring after disease on pregnancy outcomes including preterm birth, abortion (spontaneous or induced), and normal delivery. Adjustment for confounding factors including maternal age and pregnancy-disease interval were performed with the multivariable model.

Results: For women who got pregnant after disease onset, there was significantly higher risk of either preterm birth or spontaneous abortion (adjusted OR 7.31, 95% CI 1.08-49.67, p=.042). The odds increase was more prominent if PM/DM was also active during pregnancy (adjusted OR 202.31, 95% CI 4.68-8750.32,p= .006). Disease flare upon conception had been observed in 4 of 22 “post-PM/DM” pregnancies (p=.125), responded well to steroids and intravenous immunoglobulin but resulted in preterm birth or spontaneous abortion.

Conclusion: Polymyositis/dermatomyositis should be under control at pregnancy to optimize pregnancy outcome.

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APL16-1028 Idiopathic inflammatory myositis (IIM) - characteristic clinical and myositis specific antibody (MSA) phenotypes in Hong Kong Chinese patients M.H.A. Leung1 1Queen Elizabeth Hospital, Medicine, Kowloon, Hong Kong- China

Background: IIM can be phenotypically different among Western series and Chinese, and in different latitudes regions.

Objective: To explore the profile of MSA and clinical correlation of MSA in IIM patients in Hong Kong Chinese.

Method: A cross-sectional sample of 45 consecutive IIM patients seen in rheumatology specialist clinic and ward in Queen Elizabeth Hospital Hong Kong between 1-Oct-2015 and 31-Jan-2016 was recruited. ELISA testing of ENA (ENA-6 Profile, Tecan®) and MSA (Autoimmune Inflammatory Myopathies 16 Ag, Euroimmun®) was performed and clinical profile recorded.

Results: Patients characteristics were: 66% female, age 49±13 years, disease duration 8.3±5 years, 4% died during study period; 76% dermatomyositis, 22% polymyositis, 2% amyotrophic dermatomyositis. Clinical manifestations are tabulated in Table 1. Interstitial lung disease (ILD) was common (53%) and rapidly progressive ILD occurred in 7%. Malignancy occurred in 20% (2 breast cancer; one each for colon, lung, ovary, nasopharynx, prostate, thymoma and gastrointestinal stromal tumour). Table 2 shows the MSA profiles. Apart from Ro52, Jo1+ve was most common (11%) and picked up by both methods. 46% of patients had one MSA, and 9% two MSA. MDA5, PL-7, Mi2α and TIF1γ positivities were also common. Predictive values for ILD were: Jo1+ve (80%), MDA5+ve (80%) and PL-7+ve (75%). The two patients with rapidly progressive ILD were MSA-ve. Predictive values for malignancies were: SRP (100%), Mi2α (50%), TIF1γ (33%). All skin ulcers patients were MDA5+ve.

Conclusion: IIM have different clinical and immunologic phenotypes among Chinese in subtropical region. Further characterization and longitudinal follow-up studies are warranted.

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Nursing and patient education

APL16-0361 Health-related quality of life in Chinese patients with gout is associated with clinical variables and psychological disorders: a path analysis T. Fu1, R. Yin1, Q. Zhang1, L. Zhang1, L. Li1, Z. Gu2 1Nantong University, Nursing School, Nantong, China 2Affiliated Hospital of Nantong University, Rheumatology, Nantong, China

Background: Gout is the most prevalent arthritis and has a significant impact on health-related quality of life (HRQoL). There are currently no researches related to Chinese gout patients’ HRQoL.

Objectives: To identify the demographic, clinical and psychological characteristics that contribute to HRQoL in gout patients by using path analysis.

Methods: A total of 90 gout patients were recruited, completed a battery of questionnaires[a ten items of gout-related knowledge questionnaire, 36-item Short Form questionnaire(SF-36), Health Assessment Questionnaire-Disability Index(HAQ-DI) and Patient Health Questionnaire(PHQ)]. Blood samples were taken to measure serum uric acid. Correlations and path analysis was used to explore the relationships between the various predictors and HRQoL.

Results: Of the 90 patients, only 51(56.7%) and 25(27.8%) knew the disease-related and diet control-related knowledge. SF-36 score was associated with education, awareness of the disease-related and diet control-related knowledge, comorbidities, disease duration, number of swollen joints and flares, tophi, total pain, PHQ and HAQ-DI. A χ2 test indicated that the path analysis model had an adequate goodness of fit value. Pian, number of flares, PHQ and HAQ-DI were contribute directly to HRQoL, especially number of flares, PHQ and HAQ-DI. Education, awareness of the disease-related and diet control-related knowledge, disease duration, comorbidities and number of swollen joints contributed to HRQoL indirectly.

Conclusion: HRQoL in gout is mainly affected by gout-specific characteristics and psychological disorders. The data suggested that clinicians should pay more attention to the inter-related factors and make target early interventions to help patients improve their HRQoL, such as health education and psychological nursing.

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APL16-0662 Quality of life, Psychological state, and Illness Uncertainty in patients with Systemic Lupus Erythematosus C. Haoyang1, Q. Zhao2, Y. Cui2, L. Zhu1, W. Fu1, Y. He1, L. Ma1, L. Chen1, X. Wang3, B. Shen1 1The Second Affiliated Hospital of Nantong University, Nursing, Nantong, China 2The Nantong University, Nursing, Nantong, China 3The Second Affiliated Hospital of Nantong University, Rheumatology, Nantong, China

Purpose: Quality of life is an important indicator in patients with systemic lupus erythematosus (SLE).To assess the relationships between quality of Life,psychological characteristics such as anxiety and depression and illness uncertainty among patients with SLE patientis

Methods:From December 2015 to February 2016,80(age,35.84±12.59) SLE patients were consecutively invited to participate in a crosssectional study. Multiple instruments assessing Lupus Quality of Life Questionnaire (LupusQOL), hospital anxiety and depression Scale ,Mishel Uncertainty in Illness Scale,using correlation analysis and multiple regression analysis method to explore factors affecting the BIQOL in patients with systemic lupus erythematosus (SLE) .

Results:Our results showed that Dpression,anxiety , illness uncertainty,social support were accounted for quality of Life.47.5% SLE patients had anxiety, and 40% had depression. Patients who had more anxiety and depression were associated with statistically significantly lower quality of life. Patients who had more uncertainty in illness also reported significantly lower quality of life.

Conclusion: The findings of this study underscore the importance of helping patients maintain optimism,reduce illness uncertainly,because all of these factors indirectly or directly affect their quality of life.It is important and that patients likely to adopt a more pesonally plan to improve QOL.

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APL16-1075 The role of individualized nursing care to improve patient satisfaction li rheumatism lead M. Mina1, Z. Li1, W. Lijun1 1People’s Hospital of XinJiang Uygur Autonomous Region, Rheumatism immunity, Urumqi, China Objective:To further discuss the effect of the personalized nursing concept adopted to improve the patients' satisfaction in the nursing care of patients with rheumatism disease. Method: Selection 80 cases of rheumatism disease registered in our hospital from January 2015 to December 2015, divided into observation group and control group, 40 cases in each group. Control group take routine nursing, the observation group take personalized care. Results: Through data integration,the satisfaction of observation group was 95.00% (38/40), the satisfaction of control group was 82.50% (33/40), there were significant difference between two groups (P < 0.05). Conclusions: Personalized nursing concept applied to the treatment of patients with rheumatism disease, which can effectively improve patients’ satisfaction, the method is worth using for reference.

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APL16-1088 Clinical study on the application of comprehensive nursing in patients with rheumatoid arthritis Z. Li1, W. Lijun1 1People’s Hospital of XinJiang Uygur Autonomous Region, Rheumatism immunity, Urumqi, China

Objective: To observe and analyze the method and effect of comprehensive nursing for patients with rheumatoid arthritis.

Methods: selected in our hospital in January 2014 - 12 months from rheumatoid arthritis patients with a total of 621 cases (observation group) were treated by comprehensive nursing technical service and contrast 2014 300 cases of rheumatoid arthritis patients (control group) of routine nursing method and effect.

Results: in the observation group cure 323 cases, 152 cases were markedly effective, effective in 125 cases, effective rate was 96.6%, significantly higher than that of the control group (P < 0.05); mean duration of treatment (14.21 1.14 + D), shorter than that of the control group (P < 0.05); recurrence rate of 9.8%, significantly lower than the control group (P < 0.05); nursing service non normally satisfactory rate was 78.3%, 96.9% of total satisfaction were significantly higher than those in the control group (P < 0.05).

Conclusion: RA is a typical autoimmune disease and disease progression will involving multiple joints and destroy the normal joint function and structure, joint in patients with different degrees of deformity, more than pain, affect the physical and mental health. In addition to the need for comprehensive treatment of the disease, but also the need for a comprehensive care services to consolidate the efficacy, improve patient experience.

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Osteoarthritis

APL16-0020 Clinically Important Improvement Thresholds for Harris Hip Score and its ability to Predict Revision Risk after Primary Total Hip Arthroplasty J. Singh1, C. Schleck2, S. Harmsen2, D. Lewallen2 1Birmingham, USA 2Mayo Clinic, Biostatistics, Rochester, USA

Objective: To examine the clinically meaningful change thresholds, responsiveness and predictive ability of the Harris Hip Score (HHS) questionnaire.

Methods: We included a cohort of patients who underwent primary total hip arthroplasty (THA) and responded to HHS preoperatively and/or at 2- or 5-year post-THA to examine the clinically meaningful change thresholds (Minimal clinically important improvement, MCII; and moderate improvement), responsiveness (effect size (ES) and standardized response mean (SRM)) based on pre- to post-operative change and its predictive ability at 2- and 5-years post-THA for future revision.

Results: 2,667 patients with mean age of 64 years completed baseline HHS; 1,036 completed both baseline and 2-year and 669 both baseline and 5-year HHS. MCII and moderate improvement thresholds ranged 15.9-18 points and 39.6-40.1 points, respectively. ES was 3.12 and 3.02 at 2- and 5-years; respective SRM was 2.73 and 2.52. Compared to patients with HHS scores of 81-100 (score range, 0-100), patients with scores <55 at 2- and 5-years had higher hazards (95% confidence interval) of subsequent revision, 4.34 (2.14, 7.95; p<0.001) and 3.08 (1.45, 5.84; p=0.002), respectively. Compared to HHS score improvement >50 points from preoperative to 2-years post-THA, lack of improvement/worsening or 1-20 point improvement were associated with increased hazards of revision, 18.10 (1.41, 234.83; p=0.02); and 6.21 (0.81, 60.73; p=0.10), respectively.

Conclusions: HHS is a valid measure of THA outcomes, is responsive to change and predictive of revision risk post-primary THA. We have defined MCID and moderate improvement thresholds for HHS in this study.

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APL16-0284 Oral nutritional supplements for treating osteoarthritis: a systematic review and meta-analysis of randomized, placebo-controlled trials X. Liu1,2, J. Eyles1,2,3, G. Machado4, V. Ravi1,2, D. Hunter1,2 1Royal North Shore Hospital, Rheumatology, Sydney, Australia 2The Kolling Institute, Institute of Bone and Joint Research, Sydney, Australia 3Royal North Shore Hospital, Physiotherapy, Sydney, Australia 4The George Institute for Global Health, -, Sydney, Australia

Although widely used by patients with osteoarthritis (OA), the safety and efficacy of oral nutritional supplements (ONS) remain unclear and is often clouded by misinformation in mainstream media. A systematic review and meta-analysis investigated ONS for patients with hand, hip or knee OA.

Randomized controlled trials comparing ONS with placebo were eligible for inclusion. Two independent reviewers conducted study selection, assessment of risk of bias, and data extraction. Outcomes included pain, disability, stiffness, radiographic joint space width/narrowing, quality of life, analgesic use and adverse events. Data was pooled using a random-effects model and reported as standardized mean differences (SMD) or risk ratio.

71 trials identified 23 ONS in 11,021 participants with OA. Overall, no differences between supplements and placebo were demonstrated in participants reporting or withdrawal due to adverse events except for diacerein. Robust evidence demonstrated the following supplements are ineffective; -vitamin E, Sierrasil®, willow bark extract, bromelain, Artemisia annua extract, green-lipped mussel extract and eggshell membrane. The ONS demonstrating superior efficacy were boswellia serrata extract (SMD-1.6, 95%CI-2.1, -1.1), passion fruit peel extract (SMD-1.6, 95%CI-2.4, -0.9), pycnogenol (SMD-1.2, 95%CI-1.5, -0.9), curcumin (SMD-1.2, 95%CI-1.9, -0.4), and L-carnitine (SMD-1.0, 95%CI-1.5, -0.5). Avocado soybean unsaponifiables and methylsulfonylmethane demonstrated medium treatment effects. Glucosamine (SMD-0.3, 95%CI-0.5, -0.0), chondroitin (SMD-0.3, 95%CI-0.5, -0.2), and diacerein (SMD-0.4, 95%CI-0.6, -0.2) demonstrated only small treatment effects.

This evidence can be used to inform clinical decision making in this contentious area. Whereas some supplements had strong effects many widely used ONS are either ineffective or have very small treatment effects.

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APL16-0305 Stromal Cell-Derived Factor-1 (SDF-1) promotes Vascular Endothelial Growth Factor (VEGF) Expression in Chondrogenic Progenitor Cells S. Wang1, Y. Mei1, C. Zhou2, H. Zheng2, J.A. Martin2, Z. Zhang1 1The First affiliated Hospital of Harbin Medical University, Rheumatology, Harbin, China 2University of Iowa, Department of Orthopaedics and Rehabilitation, Iowa City, USA

Levels of the angiogenic peptide vascular endothelial growth factor (VEGF) are elevated in joint fluids from patients diagnosed with osteoarthritis (OA). This leads to increases in subchondral angiogenesis and tidemark invasion, a classic feature of advanced OA. Though a pathogenic role for VEGF is well-established, the mechanisms underlying its accumulation in diseased joints are less clear. In that regard, the chemokine stromal cell-derived factor-1 (SDF-1) is likely to drive up VEGF levels in that it is potent inducer of VEGF expression and is enriched in osteoarthritic synovial fluids. Chondrogenic progenitor cells (CPCs) may play an important role in this process, as they are abundant in osteoarthritic cartilage and overexpress SDF-1 and its receptor CXCR4. Here we conducted a series of experiments to determine the potential for CPCs to stimulate VEGF expression in cartilage. We first confirmed SDF-1-responsive VEGF expression in cartilage explants and showed that medium conditioned by CPCs induced VEGF expression in chondrocytes in a CXCR4-dependent manner In CPCs, exogenous SDF-1 stimulated increases in VEGF mRNA and protein, effects that were blocked by an inhibitor of CXCR4, and an inhibitor of p38 mitogen-activated protein kinase. These data indicate that CPCs induced VEGF expression in through a paracrine mechanism, and produce VEGF themselves through a self-sustaining autocrine mechanism. The findings are consistent with the hypothesis that CPCs contribute to the pathologic accumulation of VEGF in osteoarthritic joints.

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APL16-0486 Associations between endogenous sex hormones and MRI structural changes in patients with symptomatic knee osteoarthritis X. Jin1, B. Wang2, X. Wang1, B. Antony1, Z. Zhu1, W. Han1, F. Cicuttini3, A. Wluka3, T. Winzenberg1, L. Blizzard1, G. Jones1, C. Ding1 1Menzies Institute for Medical Research, Musculoskeletal Epidemiology, Hobart, Australia 2Monash University, Centre of Cardiovascular Research and Education in Therapeutics, Melbourne, Australia 3Monash University, Department of Epidemiology and Preventive Medicine, Melbourne, Australia

Background: Increased prevalence of knee osteoarthritis (OA) among postmenopausal women suggests the

involvement of endogenous hormones in pathogenesis. However, the effects of endogenous sex hormones on

knee OA structures remain uncertain.

Methods: We examined 200 participants (mean age 63.0 ± 7.3 years) from a clinical trial of vitamin D

supplement for symptomatic knee OA. Serum levels of estradiol, progesterone, testosterone and sex hormone

binding globulin were analyzed at baseline and 24 months later. Magnetic resonance imaging scans of selected

knee were obtained at both baseline and follow-up for the measurement of cartilage volume, cartilage defects,

bone marrow lesions (BMLs) and effusion-synovitis volume. Knee pain was assessed using a 100mm visual

analogue scale. Longitudinal data were analyzed using linear mixed-effects model.

Results: 107 males and 93 females were included in this study. For females, after adjustment for age, body

mass index, and vitamin D level, progesterone was associated with cartilage volume (β = 0.12 per quartile, p <

0.01). Estradiol levels were associated with lower grades of BMLs (β = -0.46 per quartile, p = 0.03), while

estradiol (β = -1.28 per quartile, p = 0.04), progesterone (β = -1.56 per quartile, p < 0.01) and testosterone (β = -

1.51 per quartile, p = 0.01) were inversely associated with effusion-synovitis volume for females. No consistent

associations were observed for males.

Conclusions: Endogenous estradiol, progesterone and testosterone may be protective for joint structural

changes in women but not men. This may contribute to observed sex differences in knee OA.

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APL16-0692 The association between height and osteoarthritis of the knee and hip joints in the Northern Finland birth cohort 1966 study M. Welling1, J. Auvinen2, P. Lehenkari3, M. Männikkö1, J. Karppinen4, P.J. Eskola1 1University of Oulu, Center for Life Course Health Research, Oulu, Finland 2University of Oulu and Oulu University Hospital, Center for Life Course Health Research and Unit of Primary Care, Oulu, Finland 3University of Oulu and Oulu University Hospital, Department of Anatomy and Cell biology and Surgery Clinic, Oulu, Finland 4University of Oulu and Oulu University Hospital, Finnish Institute of Occupational Health and Department of Physical and Rehabilitation Medicine, Oulu, Finland

Introduction: Osteoarthritis (OA) is the most common joint disease and causes serious medical, social and economic problems worldwide. However, the pathomechanisms behind OA are still poorly understood.

Aim: To investigate the association of height at the age of 31 with the incidence of knee and hip OA at following 15 years.

Methods: The participants of The Northern Finland Birth Cohort 1966 (NFBC1966) who were diagnosed with knee OA (98 men and 104 women) or hip OA (22 men and 18 women) between the ages of 31 and 46 were used as OA cases. Study subjects without knee and hip OA were used as controls (3,764 men and 4,216 women). Mean heights between OA cases and controls were compared. Cox regression analysis was performed to calculate the risk for OA in different height quartiles.

Results: Men with knee OA were 2.6 cm (P < 0.001) and women with knee OA 1.2 cm (P = 0.048) taller than controls. After adjusting for BMI, education, smoking and leisure-time physical activity at baseline, hazard ratio (HR) for knee OA in the highest quartile was 2.5 (95% CI 1.4-4.5) for men and 1.8 (95% CI 1.0-3.1) for women. No association was found between height and hip OA.

Conclusion: Height at the age of 31 was found to associate with incident knee OA during the following 15 years. The non-existing association between height and hip OA in the current study might be due to the low incidence of hip OA.

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APL16-0876 Adipose derived mesenchymal stem cells suppress chondrocyte apoptosis and matrix metalloproteinase production in osteoarthritis J. Zhou1, F. Lian1, Y. Wang2, Z. Zhan1, Y. Ye1, L. Liang1, H. Xu1, X. Yang1 1The First Affiliated Hospital of Sun Yat-sen University, Rheumatology & Clinical Immunology, Guangzhou, China 2The First Affiliated Hospital of Sun Yat-sen University, Interventional Oncology, Guangzhou, China

Background: There is increasing evidence that inflammation and chondrocyte apoptosis plays an important role in the progression of osteoarthritis. The use of mesenchymal stem cells (MSCs) is a promising strategy because of their high proliferative capacity, potential of chondrocyte differentiation and immunomodulatory effects. Unlike bone marrow MSCs, adipose derived stem cells (ADMSCs) were far more abundant and easier to obtain. Objective. We investigated the efficacy of intra-articular ADMSCs injections on a rat osteoarthritis model, elucidated the chondro-protective role and the underlying mechanism of ADMSCs. Methods: ADMSCs were injected into the knee cavities of SD rats after anterior cruciate ligament transection. Knee joint histological analysis was performed to observe articular cartilage degeneration and synovitis. Chondrocytes from osteoarthritis rats were co-cultured with ADMSCs. Matrix metalloproteinase, inflammatory cytokines and chondrocyte apoptosis were detected. PCR and western blot were used to identify the targets of ADMSCs. Results: Intra-articular ADMSCs injection attenuate rat osteoarthritis by reducing osteophyte and synovitis. Osteoarthritis chondrocyte-ADMSC co-cultures showed that MMP-13, DDR-2 and inflammatory cytokines was significantly down-regulated, and collagen II was significantly up-regulated compared to osteoarthritis chondrocyte cultures. ADMSCs suppressed inflammatory chondrocyte apoptosis. Conclusion: Our findings point to a role that ADMSCs attenuated rat osteoarthritis induced by anterior cruciate ligament transection. MMP-13 and DDR-2 plays an important role in mediating the process. Together, the data indicate ADMSCs suppress chondrocyte apoptosis trigged by inflammation.

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PAH/ILD APL16-0097 Increased Cyr61 in connective tissue disease associated pulmonary arterial hypertension involving in proliferation of pulmonary arterial smooth muscle cells L. GAO1, Y. FAN1, Y. HAO1, W. ZHOU1, Z. ZHANG1 1Peking University First Hospital, Department of Rheumatology and Clinical Immunology, Beijing, China

Objectives: To evaluate the expression of Cyr61 in connective tissue disease associated PAH (CTD-PAH) patients and investigate the effect of Cyr61 on proliferation of PASMCs in PAH rats and the mechanism.

Methods: Collecting the plasma of CTD-PAH,CTD without PAH,IPAH and healthy control patients, ELISA was used to detect the level of Cyr61.Next,specific pathogen free grade male Sprague Dawley rats were divided into monocrotaline induced PAH model group and normal control group. Lung tissues and pulmonary arteries of rats were collected and the PASMCs were dissected and cultivated. Expression of Cyr61 in the lung tissues, pulmonary arteries and PASMCs were tested by immunohistochemical staining, Western blot and Real-time PCR. Meanwhile, PASMCs from both group rats were stimulated by exogenous recombinant Cyr61 protein, Cell Counting Kit-8 was used to identify cell proliferation. At last,RNA interference (RNAi) was used to inhibit the endogenous expression of Cyr61 in PASMCs,and the expression of p-AKT and AKT and the proliferation of PASMCs were analysed.

Results: Plasma level of Cyr61 in the CTD-PAH patients were significant higher than that of CTD without PAH and healthy control. Compared with control rats, Cyr61 was overexpressed in the lung tissue and PASMCs of PAH rats. Exogenous recombinant Cyr61 protein could promote the proliferation of PASMCs from two groups of rats. While the expression of Cyr61 in PASMCs was inhibited by RNAi,cell proliferation was restrained and the expression of p-AKT declined.

Conclusions: Level of Cyr61 in the plasma of PAH patients was highly increased.Cyr61 could promote PASMCs proliferation via AKT pathway,which indicated Cyr61 may play a role in the pathogenesis of PAH.

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APL16-1185 Red blood cell distribution width as a useful indicator of pulmonary arterial hypertension in patients with systemic sclerosis J.L. Zhao1, X. Guo2, Q. Wang1, D. Xu1, Y. Hou1, M. Li1, X. Zeng1 1Peking Union Medical College Hospital, Rheumatology, Beijing, China 2Peking Union Medical College Hospital, Cardiology, Beijing, China

Objective: The aim of this study was to investigate the utility of Red blood cell distribution width (RDW) as a simple and readily available marker of PAH in patients with SSc.

Methods: One-hundred and fifty consecutive patients with SSc were recruited. Demographic characteristics, hematological parameters including complete blood count, RDW, Modified Rodnan skin score (MRSS), as well as WHO functional classifications were determined. Diagnosis of PAH was based on right heart catheterization. Cases were stratified into three groups according to the RDW tertiles (<13.6%, 13.6-14.6%, and >14.6%) and clinical relevant differences were evaluated by the ANOVA test or the Chi-square test, as appropriate.

Results: The mean age of patients was 43.6±11.5 years. PAH was detected in 28 of lcSSc (33.3%) and 14 of dcSSc subjects (23.0%). Patients with higher RDW values were more likely to be men, and had significantly higher percentage of anti-u1RNP, and PAH. A significant correlation was found

between RDW and hsCRP (p=0.375, p<0.01),and the DLCO (ρ=-0.396,p<0.01). SSc-PAH group

had significant higher RDW values compared with SSc without pulmonary disease (15.7±2.2, and 13.7±1.0, P<0.001). The ROC curve showed that RDW was a significant indicator of PAH in SSc patients (P<0.001), the optimal RDW cut-off point was 14.3% with a sensitivity of 78.6%, and specificity of 69.9%. High RDW was the independent parameter indicating PAH in patients with SSc (OR=3.314[95%CI 1.038-10.580], p<0.05).

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Conclusion Increased RDW was significantly associated with PAH, RDW could be used an independent marker to identify the pulmonary arterial hypertension in SSc patients.

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APL16-0044 Efficacy and safety of Infliximab in juvenile idiopathic arthritis and juvenile ankylosing spondylitis: A randomized, double-blind, controlled study H. Zeng1, Z. Ping1 1Guangzhou Children Hospital, Department of Pediatric Allergy- Immunology and Rheumatology, Guangzhou, China

Objective: The randomized double blind method was designed to observe the efficacy and safety of infliximab for juvenile idiopathic arthritis (JIA) and juvenile ankylosing spondylitis (JAS).

Methods: The 45 cases of this study were allocated to treatment group and control group using the randomized, double blind method. The treatment group was divided into JIA subgroups and JAS subgroup. The test groupreceived MTX combined with infliximab intravenous infusion; the control group received MTX combined an equal volume of placebo intravenous infusion.

Results: The treatment groups of this study included 12 JIA cases and 7 JAS cases while the control group included 18 JIA cases and 8 JAS cases .The ASAS 20 response rate of JAS treatment group after two weeks was 85.7% ,which was far higher than 25 % ,the rate of the control group (P = 0.04). The ASAS 20 response rate in the treatment group at the endpoint was 100%, while the rate of control group was 37.5 % (P = 0.07) .The total number of infliximab injection was 124, including 24 JIA and JAS cases. One JIA case of penicillin anaphylaxis appeared with systemic wheal -like rash during the 4th injection , and the rash subsided one hour later with the oral phenergan treatment.

Conclusion: This study shows that MTX combined with infliximab can quickly alleviate joint pain and reduce inflammatory markers compared with single MTX in the treatment of juvenile idiopathic arthritis and juvenile ankylosing spondylitis .

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APL16-0961 The Diagnostic Significance of serum IFN-γand IL-10 in Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis L. Guo1, M.P. Lu1, L.P. Teng1, L.X. Zou1, Y.P. Xu1 1Children's Hospital - Zhejiang University School of Medicine, Division of Rheumatology/ Immunology/ Allergy, Hangzhou, China

Objective To explore the diagnostic significance of interferon-gamma (IFN-γ) and interleukin (IL)-10 in macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (SJIA).

Methods In this study, 108 patients with SJIA, of 10 cases complicating MAS were enrolled. The serum cytokines including IL-2, IL-4, IL-6, IL-10, tumor necrosis factor-alphaTNF-a, and IFN-γ were determined using cytometric bead array techniques. Results Of 108 patients with SJIA that were analyzed, 10 of MAS manifested a specific cytokine pattern of highly increased levels of IFN-γ (median level: 64.1 pg/mL) and IL-10 (44.9 pg/mL) .When setting cut-off points for MAS, IFN-γ>18.4pg/mL, specificity reached 92.5%, and sensitivity was 100%, the positive predictive value andnegative predictive value reached 58.8% and 100%,respectively. When setting cut-off points for MAS, IL-10 >11.2pg/mL, specificity reached 88.2%, and sensitivity was 100%, the positive predictive value andnegative predictive value reached 47.6% and 100%,respectively. Conclusion The markedly elevated levels of IFN-γ and IL-10 had high diagnostic accuracy for MAS complicating SJIA and may be helpful for early identification of MAS.

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PsA APL16-0173 Coronary artherosclerosis in psoriatic arthritis – a case control study T.H. Cheng1, K.T. Wong2, J. Shen1, Q. Shang1, E.K. Li1, L.S. Tam1 1The Chinese University of Hong Kong, Department of Medicine and Therapeutics, Hong Kong- China 2The Chinese University of Hong Kong, Department of Imaging and Interventional Radiology, Hong Kong- China Introduction: The aim of this study was to evaluate the presence, burden and compositional differences of

coronary plaque in patients with psoriatic arthritis (PsA) without symptoms or diagnosis of coronary artery

disease (CAD) compared with controls.

Design and subjects: A total of 55 PsA patients underwent 64-slice coronary CT angiogram (CTA) and data from 55 age and gender matched control were retrived. Standardised American Heart Association 15-segment model was used for imaging analysis. Lesions were classified as noncalcified plaque (NCP), mixed (MP), and fully calcified plaque (CP).

Results: The mean age and sex (Male: 36 (65%) vs Female: 19 (35%) for both groups) of PsA patients (50±12 years) and controls (49±10 years) were similar. The proportion of PsA patients having any coronary plaque were numerically higher compared with controls (61.8% vs 47.3%, p=0.13), The prevalence of NCP appeared to be increased in PsA patients compared to controls (50.9% vs 34.5%, p=0.08). After patients were subdivided according to gender, female PsA patients have a significantly higher prevalence of NCP (9(47.4%) vs 3(15.8%), p=0.04). The increase in risk remained significant after adjusting for other risk factors (OR=6.0, 95% CI:4.1-34.3, p=0.04, table 1). With regards to PsA patients, disease duration was the only independent predictor for having NCP (OR=1.078, 95%CI=1.003-1.159, p=0.041) after adjusting for age and gender.

Conclusion: Female PsA patients were at a higher risk of developing NCP compared with controls. Inflammatory burden as reflected by the longer disease duration was probably the main driver for PsA patients to develop coronary atherosclerosis.

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APL16-0249 Safety and tolerability with secukinumab in psoriatic arthritis: Pooled safety analysis from two phase 3 randomized trials P. Mease1, I. McInnes2, P. Nash3, A. Widmer4, S. Mpofu4 1Swedish Medical Center and University of Washington, Division of Rheumatology Research, Seattle, USA 2University of Glasgow, Institute of Infection- Immunity- and Inflammation, Glasgow, United Kingdom 3University of Queensland, Department of Medicine, Brisbane, Australia 4Novartis Pharma AG, Immunology and dermatology, Basel, Switzerland

Background: Secukinumab improved signs and symptoms of psoriatic arthritis (PsA) in two randomized, double-blind, placebo-controlled phase 3 studies, FUTURE 1 and 2 (NCT01392326, NCT01752634). Here, we report the overall safety profile of secukinumab, and rate of infections using pooled data from these studies.

Methods: Safety data were pooled from FUTURE 1 and 2. Details of the study designs, efficacy and safety results of each study have been published elsewhere. All randomized patients receiving ≥1 dose of secukinumab were included in this safety analysis, with data through ≥52 weeks for FUTURE 1 and through ≥24 weeks for FUTURE 2 included.

Results: 974 patients received ≥1 dose of secukinumab (955 patient-years of exposure). Adverse event (AEs)/serious AE rates during the 16-week placebo-controlled period were 58.9%/3.4% and 58.3%/4.0% with secukinumab and placebo, respectively (Table). Throughout the entire analysis period, 24 (2.5%) patients discontinued secukinumab treatment due to AEs. One death due to intracranial hemorrhage was reported in a patient with a history of cardiovascular disease, who received secukinumab. Nasopharyngitis and upper respiratory tract infections were the most frequently reported AEs with secukinumab. No events of hepatitis viral infection, latent tuberculosis, or any other serious opportunistic infection were reported across the entire treatment period. The incidence of candidiasis, inflammatory bowel disease, neutropenia, major adverse cardiovascular events, and malignancy was low (Table).

Conclusion: Secukinumab was well-tolerated in patients with active PsA, with a low incidence of infections reported. No serious opportunistic infections, or cases of reactivation of tuberculosis or hepatitis were reported.

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APL16-0462 Switching to secukinumab improves signs and symptoms of psoriatic arthritis in patients randomized to placebo in the FUTURE-2 study P. Nash1, I. McInnes2, P. Mease3, A. Widmer4, C. Gaillez4 1University of Queensland, School of Medicine, Brisbane, Australia 2University of Glasgow, Immunology- Infection and Inflammation, Glasgow, United Kingdom 3Swedish Medical Centre and University of Washington, Rheumatology Clinical Research Division, Seattle, USA 4Novartis Pharma AG, Immnunology & Dermatology, Basel, Switzerland

Background: Secukinumab, an anti-interleukin-17A monoclonal antibody, improved signs and symptoms of psoriatic arthritis (PsA) in the Phase 3 FUTURE-2 study (NCT01752634). Herein, we report the efficacy of secukinumab in patients who were originally randomized to placebo and who subsequently switched to secukinumab.

Methods: Patients with PsA (N=397) were randomized to s.c. secukinumab 300mg, 150mg, 75mg, or placebo at baseline, Weeks 1, 2, 3, 4, and every 4 weeks thereafter. Based on clinical response at Week 16, placebo-treated patients were re-randomized to receive secukinumab 300mg or 150mg s.c. from Week 16 (placebo-nonresponders) or Week 24 (placebo-responders). Primary endpoint was ACR20 response at Week 24. Secondary endpoints included ACR50, PASI75/90, DAS28-CRP, SF36-PCS, HAQ-DI, resolution of dactylitis and enthesitis. ACR70 was an exploratory endpoint. For binary variables, missing values were imputed as non-response; continuous variables used mixed-effect model repeated measures.

Results: Of 97 patients randomized to placebo, 88 switched to secukinumab; 55 (62.5%) were placebo-nonresponders and 33 (37.5%) were placebo-responders. Clinical improvements were observed after switching from placebo to secukinumab. At Week 52, ACR20 response rates in placebo-nonresponders were 57.1% (placebo→secukinumab 300mg) and 77.8% (placebo→secukinumab 150mg), and in placebo-responders, 76.5% (placebo→secukinumab 300mg) and 56.3% (placebo→secukinumab 150mg; Figure). No consistent dose-dependence was noted regarding ACR20 response rates amongst placebo-responders or placebo-nonresponders. ACR50/70 responses rates were: placebo-nonresponders, 32.1%/21.4% and 22.2%/3.7% and placebo-responders, 58.8%/41.2% and 43.8%/18.8%, in the placebo→secukinumab 300mg and placebo→secukinumab 150mg groups, respectively.

Conclusions: Switching to secukinumab was associated with rapid improvement in signs and symptoms of PsA in patients originally randomized to placebo.

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APL16-0601 Comparation of Ultrasonic Imaging of Enthesopathy in the Lower Limbs in Patients with Psoriasis and Psoriatic Arthritis F. Sun1 1PLA General Hospital, Rheumatology, Beijing, China

Objective: To investigate the characters and differences of enthesopathy of ultrasonic imaging in the lower limbs in psoriasis(Ps) and psoriatic arthritis(PsA), to explore the risk factors of Ps developing into PsA.

Methods: Ultrasound of the lower limbs entheses was performed using a Logiq e R6 machine, with a linear probe at 4 12 MHz. A comparation of ultrasonic imaging between the three groups was made.

Results: 45 Ps, 45 PsA cases and 45 HCs who were Sex- and age-matched consecutively recruited. 230 of 450 entheses were abnormal in Ps, compared with 233 and 1

14 abnormal sites respectively in PsA and HCs(P<0.001). The presence of osteophyte, erosion and

power Doppler (PD) signal in Achilles tendon were significantly higher in PsA than Ps (P<0.05) and

HCs (P<0.01). A longer course of psoriasis was the risk factor of developing into PsA (OR =1.13, P<

0.001). The GUESS score was higher in Ps and PsA than that in HCs (P<0.01). There were no differ

ences in PASI and GUESS score between Ps and PsA. No differences were found in the presence of

enthesopathy between Ps/PsA with or without nail disease (P>0.05).

Conclusion: The frequency of enthesopathy in lower limbs was significantly higher in Ps and PsA than HCs when detected by ultrasonography. The presence of osteophyte, erosion and PD signal in Achilles tendon were significantly lower in Ps than PsA. A longer course of psoriasis may be the predictive signal of developing into PsA in the future.

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Rare Diseases APL16-0264 Difference Between Adult Onset and Juvenile Onset Behcet's Disease from the Registry of Iran’s Behcet’s Disease F. Davatchi1, F. Shahram1, C. Chams-Davatchi1, A. Nadji1, S.T. Faezi1, M. Akhlaghi1, H. Shams1, H. Kavosi1, B. Sadeghi1, A. Farimah1, M. Negin1, M. Maryam1 1Tehran University of Medical Sciences, Rheumatology Research Center, Tehran, Iran

Introduction: Behcet’s Disease (BD) is a multisystem disease, classified among vasculitides by the 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides, in the group of Variable Vessel Vasculitis. The aim of this study was to see if differences exist between Adult Onset (AOBD, first manifestation at the age ≥16 years) and Juvenile Onset Behcet’s Disease (JOBD, ≤15 years).

Materials and Methods: All patients from the registry (7414) who were diagnosed by expert opinion entered the study (96.8% were classified as BD by the new 2014 revised International Criteria for Behcet’s Disease, the ICBD). Patients were divided into 2 groups of AOBD (6190 patients) and JOBD (1224 patients). All manifestations were compared in the two groups by Pearson’s chi square test. P values inferior to 0.05 were accepted as significant differences.

Results: The following manifestations were seen more frequently in AOBD: Males 56.4% versus 51.7% (56.4/51.7), genital aphthosis (65.5/60.9), Skin manifestations (64/59) with erythema nodosum (23.9/18.5), oligoarthritis (17.7/14.5), Phlebitis (6.7/4.7), positive Pathergy test (52.3/41.1), HLA-B5 (54.3/48.3) and HLA-B51 (50.0/39.6), ESR of 20 to 40 (34.4/30.7) and 50 to 99 (14.7/11.4), and hematuria (8.0/6.4). The following manifestations were seen more frequently in JOBND: Females (48.3/43.6), ankylosing spondylitis (3/2), HLA-B27 (10.1/8.1), normal ESR (52.0/4.7), pregnancy (3.8/2.5), stable manifestations during pregnancy (2.1/1.2), familial history of BD (5.9/4.1) and aphthosis (44.9/31.4), and seronegative sponyloarthropathy (1.3/0.7).

Conclusion: Statistically significant differences were seen in 21 items (total 105). However, only the difference between 6 items were clinically relevant, having a difference of 5% or more.

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APL16-0500 Clinical features associated with higher inpatient mortality in adults with septic arthritis - A 10-year retrospective study A. Premkumar1, C. Pawa1, A. Santosa2, M. Lahiri2 1National University of Singapore, Yong Loo Lin School of Medicine, Singapore 2National University Health System, Division of Rheumatology- Department of Medicine, Singapore

Background: Septic Arthritis (SA) is associated with considerable morbidity and mortality.

Objective: We describe the clinical features and outcomes of SA in patients admitted to a tertiary hospital in Singapore over 10 years.

Methods: Electronic medical records of adult patients admitted between 2005 and 2015 with diagnostic code for SA were reviewed in detail. Diagnosis of SA was confirmed based on positive gram stain or cultures from the joint, or blood or genital swabs with clinical diagnosis of SA. Data was collected by 2 independent researchers with standardization performed on 30 randomly selected patients.

Results: 1067 patients were identified from diagnosis codes, with 249 (23.3%) confirmed to have culture positive SA. The median (IQR) age at diagnosis was 58 (46, 71) years. 64% were male. 60%, 22% and 11% were Chinese, Malay and Indian respectively.

Table 1 and 2 illustrate of the clinical features and the pre-disposing conditions, respectively, identified in these patients while Table 3 highlights the eventual treatment and prognosis.

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Using univariate logistic regression, age ≥ 70 years, high WC, absence of fever and infection with MRSA were associated with higher mortality (Table 4).

Conclusions: Staphylococcus aureus remains the most common cause of SA. Most patients in our dataset had at least one predisposing factor. There were more deaths in patients who were afebrile at presentation, possibly because the absence of fever led to a delay in diagnosing SA. Early aggressive treatment may be warranted in older patients, especially in those with higher WC or infection with MRSA.

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APL16-0549 Prevalence and peculiaritis of carditis in rheumatic fever in adult patients N. Omurzakova1, I. Moldotashev1, T. Nakajima2 1National Center of Cardiology and Internal Medicine, Rheumatology, Bishkek, Kyrgyz Republic 2Tokyo Medical University, Institute of Medical Science, Tokyo, Japan

We have studied 400 patients with rheumatic fever (RF) at the age of 15-45 years. Predisposing factors for the development of acute RF was the presence of streptococcal tonzillopharingitis 49.5%. In 72.5% of cases was formed carditis with valvulitis, chronic rheumatic heart disease (RHD). In 98 (25.0%) of them installed valvulitis mitral valve in 24 men (18.8%) and in 74 (28.4%) women. Valvulitis aortic valve was detected in 44 (33.3%) men and in 22 (8.4%) women. In 228 (58.1%) patients observed at the same time valvulitis mitral and aortic valves, while in 64 (48.8%) men and 164 (63.0%) women. In 36 (66.6%) patients with ARF was observed mitral valve prolapse (MVP), in 12 (22.2%) were in men, 24 (44.4%) in women, and 6 patients was transient, during in patient treatment. In patients with recurrent ARF was observed only 70 (20.2%) cases of MVP, 22 (6.3%) of them were men and 48 (13.8%) women. In addition, 4 patients with ARF was observed transient prolapse of the tricuspid valve with registered by boundary compaction. In 14 (3.5%) patients with ARF proceeded pancarditis (endocarditis, myocarditis and pericarditis). Symptoms of pericarditis in this group of patients manifested a slight effusion into the cavity of the pericardium. Signs coronaritis (typical anginal pain with ECG signs of ischemia, arrhythmias, heart block) were observed in 28 (7.0%) patients with RF, age was 23-39 years. If necessary, verification of diagnosis was carried out using the angiography of coronary arteries.

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APL16-1285 Ultrasound guided injection of carpal tunnel syndrome: a Comparative study to blind injection. G. Omar1, A. Ragaee1, A. Darweish1, F. Ali1 1Faculty of Medicine, Rheumatology & Rehabilitation, Minia, Egypt

Background: Carpal tunnel syndrome (CTS) is the most common upper limb neuropathy with increasing incidence especially among females, having a high economic and social impact on patients. CTS can be treated either with conservative measures or surgically. Steroid injection, as a conservative treatment, could be carried out using anatomical landmarks, or via ultra-sonographic guidance.

Aim of the study: was to compare the clinical outcomes of the ultrasound guided injection versus blinded one for management of carpal tunnel syndrome.

Thirty patients with carpal tunnel syndrome, recruited from Rheumatology and Rehabilitation outpatient clinic, Minia University Hospital, Egypt, were included in this study. Diagnosis based on clinical, electro-physiological and ultrasound imaging. According to the electrophysiological studies, there were 28 patients with moderate CTS and 2 patients with mild CTS. Patients were equally divided into two groups according to their method of injection, fifteen patients with ultrasound guidance technique and other 15 patients were injected blindly. Injection was performed once at baseline with o.5 ml of lidocaine 1% and 40 mg of triamcinolone.

Results: Evaluation at baseline and after 4 weeks of injection including Boston carpal tunnel questionnaire {symptom severity scale (SSS) and functional status scale (FSS)}, nerve conduction study, ultrasound parameters (cross-sectional area, flattening ratio) were determined and compared among methods of injection. Patients with ultrasound guided injection had significant improvement of clinical, neurophysiological, ultrasound parameters outcomes than blind injected patients.

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Rheumatoid Arthritis

APL16-0099 Clinical significance of anti-citrullinated alpha-enolase peptide 1 antibody in patients with rheumatoid arthritis M. Yang1 1Peking University People's Hospital, Rheumatology and Immunology, Beijing, China

Objective: To explore the clinical significance of anti-citrullinated alpha-enolase peptide 1(CEP1) antibody in patients with rheumatoid arthritis (RA).

Methods: One hundred and twenty-nine patients with RA were enrolled randomly. Anti-CEP1 antibody was detected by enzyme-linked immunosorbent assay(ELISA). The correlations between serum anti-

CEP1 antibody and clinical features,disease activities,laboratory examinations or X-

ray SHARP score of RA patients were investigated.

Results: ①Anti-CEP1 antibodies were positive in 83(64.3%) of 129 RA patients. Compared with patients with negative anti-CEP1 antibodies, patients with positive anti-

CEP1 antibodies had higher rates of joint deformity and bone erosion(P<0.05). The disease activiti

es were significantly higher in patients with positive anti-CEP1 (P<0.05). There were more anti-

CEP1 positive patients with elevated ESR and decreased albumin(P<0.05).② Higher rates of pulm

onary interstitial fibrosis were found in RA patients with positive anti-

CEP1 antibodies(P<0.05).③ Higher rates of positive anti-

cyclic citrullinated peptide antibodies(anti-CCP), rheumatoid factor(RF), anti-

keratin antibodies(AKA) and anti-

perinuclear factor(APF) were found in patients with positive anti-

CEP1 antibodies(P<0.05). In the patients with negative anti-

citrullinated protein/peptide autoantibodies and RF, the positive rate of anti-CEP1 antibody was 22.7%.

Conclusion: Anti-CEP1 antibody was significantly associated with joint damage, disease activity and pulmonary interstitial fibrosis.Anti-CEP1 antibody are useful in RA diagnosis and prognosis combined with other RA related antibodies.

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APL16-0346 The Therapeutic Effects of VIP and Bayll-7082 Induced Tolerogenic Dendritic Cells on Established Collagen-Induced Arthritis Mice J. Xue1, L. Liu1, J. Shen1, H. Wu1 1Second Affiliated Hospital Zhejiang University School of Medicine, Rheumatology and Clinical Immunology, Hangzhou, China

Background: Cumulative evidence has revealed tolerogenic dentritic cells (tDCs) can relieve collagen-induced arthritis in mice through T cell tolerance and suppressing of autoimmune response effect. However, a proper way to get safe and effective tDCs is still under investigation. In this study, we investigated suitable tDCs culture conditions and immune tolerance treatment effect in collagen-induced arthritis mice.

Methods: Mouse bone marrow cells were treated with GM-CSF, IL-4, asoactive intestinal peptid (VIP) and Bay11-7082 in vitro. Cell phenotypes were identified by flow cytometry and TNT-α,IFN-γ,IL-1β,IL-4 were measured by enzyme-linked immunosorbent assay. In vivo effects of tDCs on prevention of arthritis in CIA models were investigated.

Results: VIP and Bayll-7082 induced tDCs showed decreased expression of MHC-II, CD40, CD80 and CD86 and elevated production of IL-4. Transfusion of VIP and Bayll-7082 induced tDCs decreased the bone erosion score and the degree of inflammation, synovial thickening and swelling of joints detected by microMRI and pathologic examinations in CIA mice.

Conclusion: tDCs induced by VIP and Bayll-7082 show low immunogenicity and produce increased anti-inflammatory cytokines. VIP and Bayll-7082 induced tDCs ameliorate arthritis in a CIA model.

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APL16-0386 High Prevalence of BF% Obesity in Chinese Patients with Rheumatoid Arthritis: a Cross-Sectional Study J.Z. Lin1, Y.B. Chen2, X.T. Lin2, J.D. Ma1, Y.Q. Mo1, X. Wang1, L. Dai1 1Sun Yat-Sen Memorial Hospital - Sun Yat-Sen University, Department of Rheumatology, Guangzhou, China 2Sun Yat-sen University, Zhongshan School of Medicine, Guangzhou, China

Objective: To investigate the prevalence and character of obesity in Chinese RA patients.

Methods: Two hundred and forty-seven RA patients were assessed BMI, waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR). Clinical data including RA disease activity, physical function and complications were collected. Body fat percentage (BF%) was assessed by bioelectric impedance and obesity by BF% was defined as >25% for men and >30% for women.

Results: ① According to Chinese criteria of BMI, there were 19% patients with overweight and 5% with obesity. According to BF%, there was 52% patients with obesity and female RA patients had significantly higher prevalence of obesity than male patients (55% vs 31%, P=0.006, Figure 1).

②Weight, total fat mass and trunk-to-appendicular fat ratio (TAFR) were significantly higher in BF% obesity patients than normal ones (all P<0.05). The percentages of patients whose fat distributed mainly in trunk rather than appendicular extremities (TAFR >1) was also higher in BF% obesity

patients than normal ones (83% vs 43%, P<0.001, Table 1). ③According to WC, WHR and WHtR,

there were 33%, 41% and 42% patients with central obesity respectively. ④ Comparing with normal BF% patients, BF% obesity patients were older with higher disease activity indicators (ESR and CRP) and had more complications such as dyslipidemia and fat liver (all P<0.05, Table 1).

Conclusion: This cross-sectional study suggests that high prevalence of BF% obesity in Chinese RA patients especially in female patients which might be associated with disease activity.

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APL16-0399 Exosomes in the serum of RA patients prohibit apoptosis of normal HFLSs and promote the release of TNF-α and IL-1 S. Zhao1, J. Ji1, W. Xue1, Y. Wu1, Z. Gu1 1Affiliated Hospital of Nantong University, Rheumatology, Nantong, China

Objective Bone erosion and bone destruction are the characteristic features of RA. The decrease of apoptosis of human fibroblast-like synoviocytes is involved in the development of bone destruction in RA. Exosomes are important mediators of biological information, plaing a part in the development of RA. The aim of study was to find whether exosomes participate in the pathogenesis of bone destruction in RA.

Methods Serum was collected from 10 healthy people and 20 RA patients. Exosomes were extracted by Total Exosome Isolation reagent and confirmed by transmission electron microscope and western blot. Normal fibroblast-like synovioctres (HFLSs) were stimulated with exosomes. Flow cytometry was utilized to detect the alteration of cell cycle and apoptosis rate. Apotosis proteins (Bax, BCL-2 and caspase-3) were examined by wb. The concentrations of TNF-α and IL-1 in the cell supernatants were measured by ELISA.

Results Exosomes of RA patients can prohibit the cell apoptosis and promote the release of TNF-α and IL-1 from HFLSs effectively. Of these two RA groups, the abilities of bone destruction group exosomes are higher. The expressions of Bax, BCL-2 and caspase-3 in bone destruction group are also significantly higher than that in the non bone destruction group and the normal group.

Conclusions The study showed that exosomes in the serum of RA patients can prohibit the apoptosis of HFLSs and enhance the secretion of inflammatory cytokines to promote bone destruction. Exosomes play an important role in the pathogenesis of RA. Exosomes can be used as a potential predictor for early bone destruction.

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APL16-0455 Evaluation of anxiety and depression for patients with arthritis before and after treatment C. Ma1, L. Bi1, M. Xu1, X. Zhang1 1Jilin University, Department of Rheumatology and Immunology, Changchun, China

Objective To evaluate the anxiety and depression for patients with arthritis before and after treatment.

Methods 90 patients with arthritis were evaluated, among them, 35 patients suffered from rheumatoid arthritis(RA), 30 patients suffered from ankylosing spondylitis(AS), 25 patients suffered from osteoarthritis(OA). We used Hospital Anxiety and Depression Scale (HADS) to evaluate the anxiety and depression for patients with arthritis before and after treatment.

Results 1. For the patients with RA, the anxiety score was 7.46±2.34 before treatment, 3.36±2.63 after treatment; the depression score was 6.14±2.42 before treatment, 3.21±1.67 after treatment. The

scores of anxiety and depression showed significant difference before and after treatment (p<0.05).

2. For the patients with AS, the anxiety score was 3.42±1.03 before treatment, 2.84±1.86 after treatment; the depression score was 2.68±1.79 before treatment, 2.44±1.05 after treatment. The

scores of anxiety and depression were no difference before and after treatment (p>0.05). 3. For the

patients with OA, the anxiety score was 5.04±3.11 before treatment, 4.83±2.84 after treatment; the depression score was 4.96±2.67 before treatment, 4.47±2.08 after treatment. The scores of anxiety

and depression were no difference before and after treatment (p>0.05).

Conclusion Before treatment, the scores of anxiety and depression for all patients were not up to the standard of suspicious state. Among these patients, the scores of anxiety and depression were the highest for the patients with RA, and significantly decreased after treatment. The scores of anxiety and depression were no difference for the patients with AS and OA before and after treatment.

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APL16-0803 Observational Study of Tocilizumab in Active Rheumatoid Arthritis in India A. Syngle1, S. Amin2, S. Akerkar3, P. Sarma4, A. Kakkar5, B.D. Pandeyt6, V.M. Haridas7, S. Joshi8, A. Kukreja8 1Healing Touch City Clinic and Fortis Hospital, Cardio Rheuma, Chandigarh, India 2Centre for Rheumatic Diseases, Department of rheumatology, Mumbai, India 3Jivdaya Clinic, Department of Rheumatology, Mumbai, India 4Excel Centre, Department of Rheumatology, Guwahati- Assam, India 5Sir Gangaram Hospital, Department of Rheumatolgy, New Delhi, India 6Fortis Hospital, Department of Rheumatology, Noida, India 7Arthritis Superspeciality Centre, Department of Rheumatolgy, Karnatka, India 8Roche Products India Pvt. Ltd-, Department of Rheumatology, Mumbai, India

A wealth of evidence is available globally on usage of biologic such as tocilizumab, in rheumatoid arthritis (RA), however published data in India is limited. This observational study evaluating the safety and effectiveness of tocilizumab in 110 (48 prospective; 62 retrospective) Indian patients with active RA and inadequate response to non-biologic DMARDs/anti-TNFs, was therefore designed in a real world setting.

The prospective group reported statistically significant decrease in DAS28 from 6.09 at baseline to 3.28 at 24 weeks. In 60 days, 43 (97.7%) patients had reduction of 1.2 units in DAS28 score, 32 (74.4%) patients reported low disease activity in 117 days and remission occurred in 26 (60.5%) patients in 130 days. At 24 weeks, 52.9% had ACR20, 23.5% had ACR50, and 17.7% had ACR70 response in prospective group. These patients had statistically significant improvement in Patient’s Global Disease Activity (PGDA), pain, HAQ-DI, biomarkers (ESR from 57.59 to 18.89; CRP from 22.63 to 6.94) and Hb (from 10.67 to 11.29 g/dL). No safety concerns specific to the Indian population were noted.

Mean duration of treatment was 8 months demonstrating adherence to therapy in real world setting even in a non-reimbursable market like India. Incidence of infections was not significant compared to western data. ACR scores were not as prevalent as SJC, TJC, DAS28, PGDA, and VAS.

The study provides an overview of usage of tocilizumab in real world clinical setting in non-reimbursable market. Tocilizumab was well tolerated in Indian patients with efficacy and safety outcomes consistent with global population.

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APL16-0838 Artery Compliance with cardiovascular incidence in patients with rheumatoid arthritis: results from a cohort study L. Wang1, M. Zhang1, W. Tan1, F. Wang2 1The First Affiliated Hospital of Nanjing Medical University, Department of Rheumatology and Immunology, Nanjing, China 2The First Affiliated Hospital of Nanjing Medical University, Department of Cardiovascular, Nanjing, China

Objective: Cardiovascular disease resulted from atherosclerosis is one of the most common complications of rheumatoid arthritis. Here, we analyzed the profile of large artery compliance (C1) and small artery compliance (C2) in RA patients and healthy controls, and explored the possibility to use arterial compliance as a risk indicator in RA patients.

Methods: The profiling of large and small arterial compliance was analyzed in 185 RA patients and 88 healthy controls using Cardiovascular Profiling Instrument which has been proved to be a reliable and sensitive way to forecast atherosclerosis in the future. The correlations of arterial compliance and the relevant clinical data were determined in these subjects.

Results: Compared with healthy controls, levels of C1 and C2 was significantly decreased in RA patients (p<0.001). Having excluded the traditional risk factors associated with atherosclerosis, C1 and C2 decline was still a significant indicator in RA patients (odds ratio=7.411 and 10.184, respectively). Using multi-factor regression analysis to adjust traditional risk factors for arterial compliance, we found that the levels of ESR was correlated with the abnormal large artery compliance (odds ratio =1.021). The HAQ values and the usage of leflunomide were correlated with the abnormal small artery compliance in RA patients (odds ratio =1.161 and 6.170, p<0.05, respectively). Conclusion: The values of C1 and C2 were significant indicators of artery compliance with cardiovascular incidence in RA patients. ESR, the HAQ value and the usage of leflunomide are risk factors of atherosclerosis possibly. To evaluate the artery compliance is an easy and reliable method to predict atherosclerosis in RA patients.

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APL16-0909 Assessment of effect of knee joint synovial excision combined with cDMARDs on ACPA in patients with early Rheumatoid arthritis X. Li1, J. Zhao1, W. Wang1, J. Ding1, Z. Zheng1, N. Leng1, Z. Wu1, P. Zhu1 1Fourth Military Medical University, Department of Clinical Immunology, Xi'an, China

Objective: Anti-Citrullinated Protein antibody (ACPA) plays an important role in initiating effects in the pathogenesis of rheumatoid arthritis (RA). But currently, including biological agents of drug treatment were unable to reduce the titers of ACPA, this study was intends to observation the alloeosis of ACPA of arthroscopic synovium clearance combined with cDMARDs therapy in the treatment of early RA.

Methods: A total of 104 early active RA patients were randomly assigned to arthroscopic knees synovium clearance combined with cDMARD (methotrexate + leflunomide +chloroquine sulfate) (n=52) or same cDMARD strategy alone treatment group. Clinical characteristics and disease activity

including DAS28、ESR、CRP were measured at baseline, 12 weeks and 24 weeks after treatment.

Simultaneously, the titer of ACPA and treatment responses were calculated after completion of 12 weeks and 24 weeks of treatment.

Results: The baseline characteristics were similar between the two groups. The DAS28 ESR and CRP descend for the combined treatment group was significantly larger compared with the monotherapy group. the titer of ACPA in combination therapy group decreased from 465±22.3 at baseline to 143.2±15.95 and 57.2±7.68 at 12 and 24 weeks, respectively (P<0.001), however, the cDMARD alone treatment group did not show the same trend. Thus, the combined treatment group showed a better response versus the cDMARD group considering ACR 20 (67.7% vs 36.5%), ACR 40 (58.3% vs 32.5%) results.

Conclusions: arthroscopic knees synovium clearance combined with cDMARD can reduce the ACPA titer and are more effective than cDMARD monotherapy to release RA in real clinical practice.

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APL16-0944 Treat-To-Target Practice Using Online Assessment Of Disease Activity With SSDM Mobile Tools: A Cohort Study Of RA Patients In China J. Yang1, H. Wang2, X. Xin3, H. Wei4, R. Mu5, F. Zhang6, Y. Zhu7, X. Li8, Y. Jia9, Y. Liu9, M. Wang9, L. Zhang9, F. Xiao9 1Central Hospital of MianYang- Sichuan, Department of Rheumatology, MianYang, China 2JiaXing First Hospital- Zhejiang, Department of Rheumatology, JiaXing, China 3NingBo First Hospital- Zhejiang, Department of Rheumatology, NingBo, China 4Northern Jiangsu People's Hospital- Jiangsu, Department of Rheumatology, YangZhou, China 5People's Hospital- Beijing University Medical School, Department of Rheumatology and Immunology, Beijing, China 6Hebei General Hospital, Department of Rheumatology and Immunology, Shijiazhuang, China 7Weifang people's hospital- Shandong, Department of Rheumatology and Immunology, Weifang, China 8The Second Affiliated Hospital of Shanxi Medical College, Department of Rheumatology and Immunology, Taiyuan, China 9Shanghai Gothic Internet Technology Co.- Ltd., Medical Department, Shanghai, China

Background: Treat-To-Target (T2T) strategy are critical for the treatment of RA, but the Chinese doctors can hardly provide patients with a complete assessment in the clinic due to limited time.

Objectives: To explore the effectiveness of applying Smart System Of Disease Management (SSDM) in improvement of disease activity after repeated self-assessment in Chinese RA patients.

Methods: The SSDM includes both doctors’ and patients’ application. Since Aug. 2014 to Jan. 2016, 31 rheumatologists from 25 hospitals participated in the study.

Results: 636 RA patients with repeated self-assessment of DAS28 were recruited. Proportion of patients in remission, low, moderate and severe disease activity (Rem, LDA, MDA and SDA) was 19.03%, 13.36%, 45.28% and 22.33% respectively at baseline, and changed into 26.57%, 13.68%, 45.28% and 14.47% at the last assessment. The rate of T2T (DAS28≤3.2) at the last assessment was higher than that of baseline significantly (P<0.01). The rate of SDA patients for last assessment was also significantly lower than baseline (P<0.01). 65 patients made only two assessments within 151.41±86.72 (48-372) days, whose mean DAS28 was 4.20±1.28 (2.64-7.39) at baseline and improvement of that was 0.49±1.46 (-4.31-4.25) at their last assessment. There were 61 patients making more than 5 times of self-assessment during 159.98±88.10 (28-343) days. Their mean DAS28 score was 4.27±1.13 (2.61-7.19) at baseline and improvement of that was 1.12±1.34 (-1.86-4.51) at the last assessment, which was significantly better than patients who had only two self-assessments (T=2.52, P=0.013).

Conclusions: Under regular self-assessment of DAS28 using SSDM, RA patients achieved better T2T result.

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APL16-1012 CARDIAC DYSFUNCTION IN MICE WITH COLLAGEN-INDUCED ARTHRITIS L. Xu1, Y. Shi1, X. Wang1, Q. Peng1, W. Tan1, M. Zhang1, F. Wang2 1The First Affiliated Hospital of Nanjing Medical University, Department of Rheumatology, Nanjing, China 2The First Affiliated Hospital of Nanjing Medical University, Department of Cardiology, Nanjing, China

Objective: To study the alternations of cardiac dysfunction in mice with collagen-induced arthritis that would mimic both cardiac dysfunction and articular inflammation in rheumatodi arthritis (RA).

Methods: Arthritis was induced in 6 weeks old DBA/1J mice with 2 injections (at day 0 and 21) of bovine type II collagen (CII) emulsioned in complete Freund adjuvant (CFA). The cardiac function was detected by transthoracic echocardiography at week 5, 7 and 9 after immunization. At week 9 after immunization, joints and hearts were removed and histopathological analysis were determined by HE staining and Masson staining, respectively.The mRNA levels of ANP, BNP, β-MHC, α-SMA, TGF-

β1, collagen Ⅰ, collagen Ⅲ, MMP1, MMP3, MMP9, IL-6 and IL-

8 in the hearts were evaluated by real time quantitative PCR (qRT-PCR).

Results:At week 9 after immunization, CIA mice showed significant impairment in left ventricular function, as evidenced by reduced ejection fraction and fractional shortening, increased left ventricular end-systolic volume (LVESV) and end-systolic diameter (LVESD), as well as cardiac fibrosis, and no clear differences in LV structure or function between normal and CIA mice at week 5 and 7. Furthermore, the expression of ANP, BNP, β-

MHC, α-SMA, TGF-β1, collagen Ⅰ, collagen Ⅲ, MMP1, MMP3, MMP9, IL-1β and IL-

6 in heart was markedly increased at week 9 after immunization in CIA mice compared with normal controls.

Conclusion: CIA mice displayed a significant impairment in left ventricular function characterised by cardiac hypertrophic and fibrosis, and CIA mice might be a pertinent model to study the mechanisms of cardiac dysfunction in RA.

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APL16-1034 Follicular helper T cell higer expressed and provide a biomarker for active Rheumatoid arthritis C. Xiaomei1, H. Jing2, L. Zhanguo2, W. Lijun1 1People’s Hospital of XinJiang Uygur Autonomous Region, Rheumatism Immunity, Urumqi, China 2Peking University People's Hospital, Department of Rheumatology and Immunology, Peking, China

Objective: The aim of this study was to examine the role of CCR7loPD-1hi Tfh cell subset in circulation of patients with Rheumatoid arthritis (RA), and monitored in the blood to provide a reliable biomarker for active RA.

Methods: A total of 41 patients with RA who were without treatment in three months or newly diagnosis and 32 health control were enrolled in study.All patients fulfilled the 2010 ACR/EULAR classification criteria. Clinical data were collected at same time points as the blood sample. The frequencies of CD4+CCR7loCXCR5+PD-1hi T cells was determined by flow cytometry of peripheral blood from all subjects, and the values were compared with disease activity as determined by DAS28 score.

Results: The mean age of patients was 56.1±14.0 years (range 20-82 years), the media disease duration was 6 years (range 0.1-30 years). There are no significant difference between RA patients and health control with age and gender. As compared with health control, the frequency of CD4+CCR7loCXCR5+PD-1hi T cells in RA patients is 12.8±5.7%, significantly higher than health controls (8.7±2.0%). Moreover, the frequency of CD4+CCR7loCXCR5+PD-1hi T cells in the peripheral blood correlated with DAS28 score (χ2=16.875, P<0.001). However, there are no significant statistics meaning between CD4+CCR7loCXCR5+PD-1hi T cells with anti-CCP antibodies, RF, IgG, IgA and IgM.

Conclusion: CD4+CCR7loCXCR5+PD-1hi T cells is associated with disease activity and is a valuable marker of the activity in RA. They also present a potential pathogenesis in the development of RA and target for future therapies.

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APL16-1170 Multi Biomarker Disease Activity score and its application in rheumatoid arthritis Z. Song1, Z. Zhang1 1Peking University First Hospital, Rheumatology and Immunology, Beijing, China

Recently, the promotion of Treat to Target has significantly improved the outcome of rheumatoid arthritis patients. Thus it is important to make continuous effort to find a better assessment of disease activity.

It is proved that cytokines largely contribute to the pathogenesis of RA. A new assessment of disease activity in terms of cytokines might be an objective measurement for RA disease activity. Michael Centola et al chose 12 biomarkers, including EGF, VEGF-a, leptin, resistin, IL-6, SSA, CRP, VCAM-1, MMP-1, MMP-3, TNFR1, YKL-40 etc, to measure the disease activity, which is called Multi-Biomarker Disease Activity (MBDA) score.

BeSt study revealed that MBDA score was significantly associated with DAS28-ESR, SDAI, CDAI,HAQ and ACR/EULAR Boolean remission standard. CAMERA study proved that MBDA score was significantly associated with DAS28-CRP.

SWEFOT study indicated that patients with a low to medium disease activity of baseline MBDA score had a relatively low possibility of imaging-based progression after one year of follow-up. The Leiden early arthritis cohort discovered that 93% MBDA remission patients had no imaging-based progression after a year, and was significantly different with 70% MBDA non-remission patients (p=0.001). In DAS28-CRP remission patients, those with high MBDA score had 2.3 folds risk of imaging-based progression in a year.

In 2013, Wanying Li proved that 38 patients (38%) modulated their treatment according to MBDA score, and 63% changed the treatment when MBDA score was not or partly corresponding to physicians’ assessment. MBDA score is advanced in disease activity assessment, predicting radiographic outcome and guide the management, which needs further study.

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APL16-1255 Rheumatoid arthritis patients have more autoimmune disease family histories than healthy controls Z. Yao1, R. Liu1, J. Zhang1, N. Xu1, C. Li1, J. Zhao1, X. Liu1 1Peking University Third Hospital, Department of Rheumatology, Beijing, China

Objective: To determine if the prevalence of autoimmunity among relatives of patients with rheumatoid arthritis is higher than that among relatives of healthy control s.

Methods: 100 rheumatoid arthritis patients and 50 sex and age-matched controls were included. The following autoimmune diseases were interviewed in the 892 relatives of 100 rheumaotid arthritis patients and 461 relatives of 50 healthy controls : ankylosing spondylitis, dermatomyositis, Hashimoto thyroiditis, insulin-dependent diabetes mellitus, multiple sclerosis, psoriasis, systemic sclerosis, RA, systemic lupus erythematosus, and vitiligo. Chi-squares odds ratios (ORs) were calculated.

Results: Of all the relatives of the patients, 36 had at least 1 autoimmune disorder, compared with 2 relatives of the controls (4% versus 0.4%; OR 9.64, P < 0.000001).

Conclusion: These data demonstrate that the prevalence of autoimmunityis significantly higher among relatives of RA patients. This suggests that different autoimmune phenotypes may share common genotypes.

Page 58: APLAR 2016 Oral Abstracts

APL16-1239 Characteristics of rheumatoid arthritis patients at first presentation to a specialized rheumatology department A.S. Vij1, A.N. Malaviya2, S. Kumar3 1Punjab Institute of Medical Sciences, Medicine, Jalandhar, India 2A&R’ Clinic for Arthritis & Rheumatism’ and Department of Rheumatology- ISIC Superspeciality Hospital- Vasant Kunj- New Delhi, Rheumatology, New Delhi, India 3Columbia Asia Hospital- Bangalore, Rheumatology, Bangalore, India

Background: Rheumatoid arthritis (RA) is a chronic, progressive, debilitating, systemic, autoimmune disease that mainly affects the diarthrodial joints. It is the most common inflammatory arthritis that occurs in approximately 1% of adults. The objective was to study the characteristics of patients with RA at first presentation to a specialized rheumatology department.

Methods: The study included 122 consecutive patients with RA, fulfilling 1987 American College of Rheumatology (ACR) criteria for RA at ‘Joint Disease Clinic’ of rheumatology department, at ISIC, New Delhi.

Results: The mean age was 45.3 ± 12.4 years, F:M ratio, 8.4:1; maximum patients (31.1%) were aged group 30-40 years. Mean age at onset of symptoms was 38.1 ± 12.9 years and disease duration mode 5 years. 88% patients were literate and 59% referred by other patients. 14.8% patients had family history of RA, 7.38% (all males) were smokers. 16.4% female patients developed symptoms of arthritis within one year after delivery. 44.3% patients had severe, 50.8% moderate, 3.3% mild and 1.6% inactive disease on DAS 28[ESR]. Only 8.2% patients were being treated by rheumatologists. Methotrexate and glucocorticoids were the most prescribed drugs (50.8% each) but inappropriately. 23.8% patients had co-morbidities, hypothyroidism (9%) being the commonest.

Conclusions: RA affects mainly middle aged women and hypothyroidism being the commonest co-morbidity. Most patients receive inappropriate treatment and consult a rheumatologist late, often with deformities. Hence, increased awareness is needed about this disease amongst patients and doctors so that patients get timely referral to a rheumatologist for its proper management.

Page 59: APLAR 2016 Oral Abstracts

Rheumatoid arthritis – non-TNFα biological therapies APL16-0471 REPAIR OF BONE EROSION IN RHEUMATOID ARTHRITIS BY DENOSUMAB : AN HR-PQCT STUDY J. YUE1, J.F. Griffith2, L. Shi3, D. Wang2, J. Shen4, P. Wong4, E.K. Li4, T.K. Li4, T.Y. Zhu5, V. Hung5, L. Qin5, L.S. Tam4 1The Prince of Wales Hospital- The Chinese University of Hong Kong, Department of Medicine & Therapeutics-Rheumatology, Hong Kong- China 2The Prince of Wales Hospital- The Chinese University of Hong Kong, Department of Imaging and Interventional Radiology, Hong Kong- China 3The Prince of Wales Hospital- The Chinese University of Hong Kong, Department of Medicine & Therapeutics, Hong Kong- China 4The Prince of Wales Hospital- The Chinese University of Hong Kong, Department of Medicine & Therapeutics- Rheumatology, Hong Kong- China 5The Prince of Wales Hospital- The Chinese University of Hong Kong, Bone Quality and Health Center of the Department of Orthopedics & Traumatology, Hong Kong- China Objectives: To compare the effect of denosumab and alendronate on erosion healing in female RA patients with low bone mass using HR-pQCT.

Methods: This is a post-hoc analysis of a randomized-controlled trial. 40 patients with bone erosions were randomized in a 1:1 ratio to receive either subcutaneous denosumab (60mg) once or oral alendronate (70mg) weekly for 6 months. The size and the degree of marginal osteosclerosis of bone erosions around the second metacarpophalangeal joint of the non-dominant hand were measured both semi-quantitatively and quantitatively at baseline, 3- and 6-months.

Results: At baseline, the mean (±SD) width, depth and volume of the bone erosions was similar for both groups (Table). At 6 months, erosion size significantly decreased in the denosumab group, and significantly increased in the alendronate group. The between group differences in all size criteria were statistically significant at 6 months (all p<0.01). The degree of marginal osteosclerosis was similar between both groups at baseline. After 6 months, 17/21 (81.0%) and 9/21 (42.9%) erosions in the denosumab and alendronate group respectively showed evidence of marginal osteosclerosis. Quantitative analysis showed that the BMD of the erosion margin significantly increased only after denosumab treatment (denosumab: 15.8 mg/cm3, p<0.05, alendronate: -4.7 mg/cm3, p=0.51, between group differences: p<0.05).

Conclusions: Bone erosions in RA patients treated with denosumab show evidence of repair in contrast to bone erosions in patients treated with alendronate, indicating a favourable impact of RANKL inhibitor on local bone remodeling.

Page 60: APLAR 2016 Oral Abstracts
Page 61: APLAR 2016 Oral Abstracts

Sjorgren Syndrome (PSS)

APL16-0132 IL-27 deficiency aggravates Sjogren’s syndrome through upregulating Th17/Treg ratio J. Qi1, B. Shi1, Z. zhang1, R. Feng1, W. Chen1, W. Li1, X. Tang1, G. Yao1, Y. Hou1, L. Sun1 1The Affiliated Drum Tower Hospital of Nanjing University Medical School, Department of Rheumatology and Immunology, Nanjing, China

IL-27 participates in multiple autoimmune diseases by regulating T lymphocyte subsets. Recent studies showed that IL-27 was involved in anti-inflammatory functions in SS. However, the underlying mechanism of IL-27 in SS is still unknown. Therefore, in this study, the changes of lymphocyte subsets were studied in IL-27 knock-out (Il-27-/-) and wild-type (WT) pSS models and pSS patients for the purpose to explore the specific mechanism of IL-27 in pSS and provide the basis for clinical treatment.

Compared to WT NOD mice, the saliva flow rates decreased significantly, and the weights of submandibular glands and spleens increased significantly in Il-27-/- mice. The histological results showed that the number of lymphocytic infiltrates in submandibular glands of WT NOD mice was less than Il-27-/- mice. The splenic Treg cells decreased significantly, but the levels of splenic Th17 and B cells increased significantly in Il-27-/- mice. After IL-27 treatment, the clinical indexes, Treg and Th17 cells were partially reversed in Il-27-/- mice. Compared with healthy control, the serum IL-27 decreased in pSS patients. Consistent with above observations, the changes of Treg and Th17 cells in pSS patients showed similar pattern. These findings indicated that IL-27 deficiency deteriorated the disease symptoms of pSS and resulted in disruption of Th17/Treg balance. In addition, pSS patients showed similar lymphocyte imbalance. Our data suggested that IL-27 might play an important role in the development and pathogenesis of pSS through regulating Th17/Treg balance, and targeting IL-27 may be a new direction of pSS treatment.

Page 62: APLAR 2016 Oral Abstracts

APL16-0139 IL-12 exacerbates Sjogren’s syndrome through inducing lymphocyte infiltrations into salivary glands and imbalance of lymphocyte subsets B. Shi1, J. Qi1, R. Feng1, Z. Zhang1, W. Chen1, W. Li1, X. Tang1, G. Yao1, L. Sun1 1The Affiliated Drum Tower Hospital of Nanjing University Medical School, Department of Rheumatology and Immunology, Nanjing, China

Primary Sjogren’s syndrome (pSS) is characterized by inflammation and functional impairment of exocrine glands, accompanied by the immune system disorders, including increased pro-inflammatory cytokines, decreased anti-inflammatory cytokines, and disturbed immune cell homeostasis. IL-12 is a pro-inflammatory cytokine related to autoimmune diseases. However, the role of IL-12 in pSS and the underlying mechanism are still not clear. We aimed to explore the role of IL-12 in the pathogenesis of pSS. NOD mice were treated with recombinant IL-12, anti-IL-12 mAb or saline, respectively. The salivary flow rate was determined. Histopathology of submandibular gland, lacrimal gland, lung and kidney were examined. Immunochemistry was performed to study the phenotype of the infiltrated lymphocytes. Spleen lymphocyte subsets were analyzed by flow cytometry. The results showed that IL-12 levels were significantly higher in pSS patients. IL-12 treatment significantly increased salivary gland swollen severity, reduced salivary flow rates, and promoted lymphocyte infiltration in salivary glands, pulmonary interstitium and renal medulla. Most of the infiltrated lymphocytes were CD4 positive, and majority of the CD4+ cells were secreted IL-17A. Whereas, neutralization of IL-12 not only decreased the percentages of Th1, Th17 and Tfh cells, but also corrected the imbalance of Th1/Th12 and Th17/Treg ratio. What’s more, the salivary gland swollen and lymphocyte infiltration were also reduced and were salivary flow rates increased. These findings indicated that IL-12 deteriorated pSS partially by promoting lymphocyte infiltration in the affected organs and disturbance of lymphocyte subsets. Targeting IL-12 might be a potential therapeutic strategy for SS patients.

Page 63: APLAR 2016 Oral Abstracts

APL16-0242 The effect of mesenchymal stem cells on Sjögren’s-like mice and their MicroRNAs expression profiles of splenic CD4+ T cells T. Jiangping1 1Tongji Hospital of Tongji University, Rheumatology, Shanghai, China

Background & objectives: Mesenchymal stem cells (MSCs) has immunoregulatory function and offer a promising new treatment for some autoimmune disease. This study investigate the therapeutic effect of human umbilical cord mesenchymal stem cells (UC-MSCs) on mice with relatively late stage of Sjögren’s-like disease and the impact of UC-MSCs on MicroRNAs (miRNAs) expression profiles of splenic CD4+ T cells.

Methods: Female NOD/Ltj mice were randomized into two groups as disease group and MSCs treated group, female C57BL/6 mice served as healthy group. Water intake, blood glucose and salivary flow rate were measured. Submandibular glands stained with hematoxylin and eosin to calculate the focus score. IL-2, IL-6, HGF, IFN-γ, IL-10, PEG2, TGF-β1 and TNF-α concentration in serums were measured by ELISA. MicroRNAs of splenic CD4+ T cells were measured by deep sequencing.

Results: UC-MSCs treatment prevented the salivary flow rate decline and lymphocytes infiltration in salivary glands of NOD mice, altered the cytokines/growth factors concentration in serums and miRNAs expression profiles of splenic CD4+ T cells.

Conclusions: UC-MSCs treatment had therapeutic effect on NOD mice with relatively late stage of Sjögren’s-like disease and could alter the miRNAs expression profiles of splenic CD4+ T cells.

Page 64: APLAR 2016 Oral Abstracts

APL16-0463 Impact of total glucosides of paeony on plasmacytoid dendritic cells in patients with primary Sjögren’s syndrome G. Wang1, X. Li1, X. Li1, X. Li1 1Affiliated Anhui Provincial Hospital - Anhui Medical University, Rheumatology & Immunology, Hefei, China

Objective: In primary Sjögren’s syndrome (pSS),plasmacytoid dendritic cells (pDCs) are decreased in peripheral blood and accumμl ated in salivary glands, total glucosides of paeony (TGP)could attenuate DC maturation in vivo. We thus investigate the effect of TGP on pDCss in new pSS patients and its mechanism of anti-inflammatory effects.

Methods: 17 new pSS without any treatment were recruited as disease group, accepted total glucosides of paeony for 3 months,17 healthy subjects as control group.The percentage of peripheral

blood pDCs、circulating plasma IFN-α、IL-6、TNF-α levels were analysed by Flow cytometry and

ELISA. Immunohistochemistry method has been used to observe pDCs infiltration in labial gland.

Results: New pSS patients had significantly lesser pDCss in PB,and CXCR4 expressed by pDCs were higher than healthy controls.TGP could inhibited pDCs actiition and then reduced CXCR4

expression.Plasma IFN-α、IL-6、TNF-α levels of new pSS are increased, TGP reduce IL-6、TNF-α

levels.Moreover, pDCs are present in labial gland of pSS under the effect of chemokines receptor CXCR4.

Conclusion: Our findings reveal that activated pDCss transfer to the labial gland under the effect of chemokines receptor CXCR4.Total glucosides of paeony inhibited the activation of pDCss in primary Sjögren’s syndrome.

Page 65: APLAR 2016 Oral Abstracts

APL16-0686 The clinical characteristics of primary Sjögren’s syndrome with neuromyelitis optica spectrum disorder Y. Zhao1, X. Li1, X. Huang1, F. Kong1, L. Su1, Q. Liao1, Z. Tian1, X. Li1 1Xuanwu Hospital - Capital Medical University, Rheumatology and Allergy, Beijing, China

Primary Sjögren’s syndrome (pSS) often coexists with neuromyelitis optica spectrum disorder (NMOSD). The exact relationship between these two diseases is still unclear. Our present study aimed to analyze the clinical characteristics of pSS with NMOSD. We retrospectively reviewed the medical records of 132 patients who were admitted to Xuanwu Hospital, Capital Medical University from 2011 to 2015. All of patients were diagnosed with NMOSD. Of them, 29 patients were identified as having pSS (pSS/NMOSD), and 103 patients had no rheumatic diseases except NMOSD (nrNMOSD). Compared with nrNMOSD, the patients with pSS/NMOSD had a shorter duration of disease (13.2±16.1 vs 26.2±54.2, p=0.035) and higher prevalence of autoantibodies (ANA, anti-SSA, anti-Ro52 and anti-SSB) (p<0.001). 94.1% patients with pSS/NMOSD were anti-aquaporin-4 (AQP4) positive, which was higher than that with nrNMOSD (72.4%), although the difference did not reach the statistical significance (p=0.055). We also analyzed the favorite sites of involved central nerve system (CNS) according to MRI in these patients. Interestingly, compared to nrNMOSD patients, the damage of lumbar spinal cord seemed to be more common in the patients with pSS/NMOSD (13.8% vs 1.9%, p=0.007). Conversely, the damage of brain was more common in nrNMOSD patients than in pSS/NMOSD patients (53.4% vs 44.8%, p=0.057). In conclusion, the patients with pSS/NMOSD have short duration of disease, high prevalence of autoantibodies and special damage sites of CNS, which might be distinguished from common NMOSD.

Page 66: APLAR 2016 Oral Abstracts

Systemic lupus erythematosus, Sjogren’s and antiphospholipid syndrome – clinical aspects, comorbidities and complications APL16-0473 SMS1/2 transcript abnormally in SLE patients, especially accompanied with thrombocytopenia or leukocytopenia C. Wang1, M. Sun1, Y. Zhu1, L. Dong1 1Tongji Hospital - Huazhong University of Science and Technology, Department of Rheumatology and Immunology, Wuhan, China

Objectives: Ceramide derivative can be used to treat autoimmune disease, which was also effective in a murine model of SLE. Ceramide can be metabolic via SMS1 and SMS2. We aimed to compare the expression of SMS1/2 in SLE patients and evaluate the association between SMS1/2 and disease activities as well as lmmunological abnormalities.

Methods: The mRNA expression of SMS1/2 from 35 SLE patients and 15 healthy controls were detected by RT-PCR. Systemic lupus erythematosus disease activity index (SLEDAI), ESR and immunological indexes (anti-dsDNA antibody, IgG, IgA, IgM, C3, C4) were also assessed in these patients.

Results: The levels of SMS1 as well as SMS2 in SLE patients were all significantly higher than healthy controls, although both of them were not correlated with SLEDAI (4.65±7.74 vs. 1.63±1.10, P<0.05; 5.05±7.43 vs. 1.70±1.69, P<0.05). The expression of SMS1 and SMS2 were reduced significantly in SLE patients with thrombocytopenia or leukocytopenia (P<0.01; P<0.05). The levels of SMS1 in patients without anti-ds-DNA antibody were increased obviously than the group with positive antibody (P<0.05). What’s more, the SMS1 levels were positively correlated with the serum IgA titer (r=0.453, P<0.01).

Conclusions: The levels of SMS1 and SMS2 are higher in SLE patients, and to some extent, SMS1 can reflect the hematologic involvement and immune abnormalities.

Page 67: APLAR 2016 Oral Abstracts

APL16-0611 Classification criteria for neuropsychiatric systemic lupus erythematosus: the discussion continues! S. Monov1, D. Monova2, R. Rashkov1, R. Shumnalieva1 1Medical University – Sofia- Bulgaria- Clinic of Rheumatology-, Department of Internal Medicine, Sofia, Bulgaria 2Medical University – Sofia- Bulgaria- Medical Institute – MVR, Department of Internal Medicine, Sofia, Bulgaria

Background: We present the results from our study of neuropsychiatric manifestations in 225 Systemic lupus erythematosus (SLE) patients. Based on these results we propose a new set of criteria for NPSLE. The use of these criteria for the last 5 years in Bulgarian SLE patients proved their high sensitivity and specificity.

Methods: In order to determine the type and incidence of nervous system (NS) damages clinical, laboratory, and instrumental examinations were performed in a total number of 225 SLE patients for a total period of 9 years. Depending on the specific features of the clinical course the patients were divided into three groups: with clinically manifested NS damages, without clinically manifested NS damages and with incomplete SLE. Patients with rheumatoid arthritis and healthy controls matched for age and gender were used as controls.

Results: 64.44% of the SLE patients had neuropsychiatric manifestations, 49,33% had cognitive dysfunctions. According to the proposed set of criteria the diagnosis of NPSLE should be made in the presence of at least one indicator from the first group of criteria (seizures, psychosis, cerebrovascular event, lesion of cranial nerves, motor disturbances, quantitative alterations of consciousness) and at least two indicators from the second group of criteria (cognitive dysfunction, headache due to lupus, peripheral neuropathy, MRI changes, EEG changes, ENMG changes, positive aRPA, positive aPL) after excluding other causes than SLE for their occurrence.

Conclusions: The use of the proposed criteria of NPSLE with high specificity and sensitivity allows earlier detection of NS damages and introduction of pathogenic treatment.

Page 68: APLAR 2016 Oral Abstracts

APL16-0684 A study of clinical & pathological parameters and treatment outcomes in subjects of lupus nephritis with crescent M. Rathi1, G.V. Teja1, A. Sharma2, R. Nada3, K.L. Gupta1 1Postgraduate Institute of Medical Education & Research, Nephrology, Chandigarh, India 2Postgraduate Institute of Medical Education & Research, Rheumatology, Chandigarh, India 3Postgraduate Institute of Medical Education & Research, Histopathology, Chandigarh, India

Introduction: Crescentic lupus nephritis (CLN) is the most severe form of renal involvement in systemic lupus erythematosus (SLE). We aim to study the significance of crescents on the presentation and treatment outcomes and the factors associated with outcomes.

Materials & Methods: Renal biopsy confirmed lupus nephritis cases were included and divided into four subgroups: Control Group (no crescents), Group 1 (<25% crescents), Group 2 (25%-50% crescents), and Group 3 (≥50% crescents). Clinical details were noted, and the renal biopsy was reviewed for type of crescents, underlying glomerular changes, activity and chronicity indices, tubulointerstitial and vascular damage. Outcomes were assessed at the end of six months.

Results: A total of 150 patients (136 females, 14 males) with mean age of 31.2 ± 10.23 years were included. Of these, 85 (56.7%) were in control group, 31(20%) in group 1, 13 (8.7%) in group 2 and 21 (14%) in group 3. Group 3 patients had more rapidly progressive renal failure, high serum creatinine (p = 0.001), high activity and chronicity indices (p <0.005), without any significant difference in proteinuria or disease activity. Treatment failure and death were more and complete remission was less in group 3 at follow-up. On linear regression, cellular and fibrocellular crescents were independent predictors of initial and follow-up serum creatinine (p <0.005), while fibrous and fibrocellular crescents were independent predictors of follow-up proteinuria.

Conclusion: CLN was associated with more severe renal presentation and poor treatment outcome. The severity of presentation and adverse treatment outcome increases with increase in percentage of crescents.

Page 69: APLAR 2016 Oral Abstracts

APL16-0784 Posterior Reversible Encephalopathy Syndrome and Subarachnoid Hemorrhage after Methylprednisolone Pulse Therapy for a Patient with Lupus Nephritis I.E. Afos1 1Section of Rheumatology, Department of Medicine, Manila, Philippines

Background: SLE is a chronic inflammatory disease that can affect any organ including the nervous system. Subarachnoid hemorrhage (SAH) is one of its rare CNS manifestations.1 Posterior Reversible Encephalopathy Syndrome (PRES), with features of headache, seizures, altered mental status, visual loss and typical imaging findings, has recently been associated with SLE and immunosuppression, including use of high dose steroids.

Setting: University of the Philippines-Philippine General Hospital

The Case: We report a case of 33 year-old female with lupus who had PRES and SAH after Methylprednisolone Pulse Therapy (MPPT) for nephritis. She presented with headache, hypertension and seizure. Initial cranial imaging showed hypodense areas in both parietotemprooccipital regions and small acute infarcts. She was intubated and treated with anti-convulsants for seizure; hydrocortisone and mycophenolate mofetil for SLE. She was extubated fully conscious on the 7th hospital day. On the 11th hospital day, she developed fever, cough and was noted to be drowsy. She had anasarca and azotemia. Repeat cranial CT scan showed SAH at the right Sylvian fissure and better delineation of parietotemporooccipital hypodensities (consistent with PRES). She was treated for hospital acquired pneumonia and underwent hemodialysis. Patient became conscious with no recurrence of seizure. Consecutive outpatient visits showed a conscious and less edematous patient. Anti-seizure medications as well as hemodialysis were discontinued. Cranial CT scan a year later revealed normal brain parenchyma.

Significance: There is a need to recognize PRES and differentiate it from irreversible neurologic conditions. With early identification and prompt intervention, permanent neurologic deficits may be prevented.

Page 70: APLAR 2016 Oral Abstracts

APL16-1138 Clinical factors associated with microstructural brain volume atrophy in non-neuropsychiatric systemic lupus erythematosus patients Y. Zhao1, Y. Cheng2, Z. Xie1, A. Lai1, Z. Lv1, J. Xu1 1First Affiliated Hospital of Kunming Medical University, Department of Rheumatology and Immunology, Kunming, China 2First Affiliated Hospital of Kunming Medical University, Department of Psychiatry, kunming, China

This study was performed to characterize changes in gray matter and white matter volumes between patients with systemic lupus erythematosus (SLE) and matched controls using structural magnetic

resonance imaging, between patients with and those without neurocognitive deficit;and in relation to

clinical characters. Eighty-nine NPSLE patients without obvious cerebral deficits as judged by conventional MRI, as well as 84 healthy control subjects, underwent high-resolution structural MRI scans in this study. The whole-brain volume of grey matter (GMV) and white matter (WMV) were calculated for each individual and the correlations between brain volume and clinical characters were also analyzed. We found obvious GMV and WMV reduction of the SLE group compared with controls. WMV of patients who received immune suppressive treatment showed less volume reduction than those of patients who never received such treatment. A positive correlation between WMV and total steroid was also identified. Compared with male patients and healthy controls, female patients had the more obvious GMV and WMV reduction. Association between WMV with cognitive impairment, and GMV with depression symptoms were found. No significant relationship between the volume reduction and the autoantibodies were identified. Thus the obvious brain microstructural atrophy can happen even before emergence of significant symptoms and deficits in central nervous system. The sex difference of GMV/WMV reduction, as well as the more sensitive changes of WMV related to cumulative steroid use, suggested the complicate and different underlying mechanisms for gray and white matter alterations.

Page 71: APLAR 2016 Oral Abstracts

Systemic lupus erythematosus, Sjogren’s and antiphospholipid syndrome – therapies APL16-0407 The efficacy of Rituximab in refractory systemic lupus erythematosus associated thrombocytopenia: a systemic review of literature J. Huang1, Y. Li1, X. Zuo1 1Xiangya Hospital of Central South University, Rheumatology, Changsha, China

Background: Thrombocytopenia is one important complication of systemic lupus erythematosus (SLE), with high incidence and recurrence rate. Rituximab has been successfully used in the treatment of SLE associated thrombocytopenia, where immunosuppressors have failed. But the best dosage and the actual efficacy of this therapy are still obscure.

Method: We analyzed 8 person-time Rituximab usages for SLE associated thrombocytopenia in our hospital from 2009 to 2016. Gathering up all the cases documented in the literature, we got totally 92-person-time Rituximab usages in SLE associated thrombocytopenia for statistical analysis. According to the difference of therapeutic regimen, we divided these cases into 2 groups, with one recommended regimen group and another relatively low-dose regimen (widely used in China) group, then compared their efficacies.

Result: The remission rate of Rituximab is 84.8% (78/92), with 67.4% (62/92) complete remission (CR) and 17.4% (16/92) partial remission (PR). The median onset time is 1 month. While its recurrence rate is 13.4% (9/67), with the median reccurence time 5 months. Interestingly, the relatively low-dose regimen appeared no less effective than the recommended one, with CR rate and PR rate (92.0% and 8.0% vs. 58.2% and 20.9%). However, it showed a higher recurrence rate than the latter one (28.0% vs. 4.8%), with the quartile recurrence time 3 to 6 months for both groups.

Conclusion: Rituximab is a promising alternative therapy for refractory SLE associated thrombocytopenia. The widely used low-dose regimen in China seems as good as the recommended one, only with a slightly increase in the recurrence rate.

Page 72: APLAR 2016 Oral Abstracts

APL16-0531 Glomerular chemokine expression in murine lupus nephritis T.A. Kadiombo1, H. Ikeuchi1, J. Suwa1, A. Maeshima1, T. Sakairi1, Y. Kaneko1, K. Hiromura1, Y. Nojima1 1Gunma University, Medicine and Clinical Science, Maebashi, Japan Background/Purpose: Although chemokines are thought to play a crucial role in recruiting inflammatory cells to local diseased sites, little is known about profiles of glomerular chemokine expression in lupus nephritis. The objective of the current study is to explore the profiles of chemokine gene expression in isolated glomeruli from lupus-prone mice and to examine their relationship with infiltrating inflammatory cells and glomerular damages.

Methods: Glomerular expressions of CCL-2, CCL-5, and CXCL-10, which are potent chemotractants for T cells and monocytes, were examined with real-time polymerase chain reaction after purifying glomeruli using the magnetic microbead method from lupus-prone MRL/lpr mice and control MRL/+ mice. Infiltrating T-cells and monocytes in glomeruli were detected by immunohistochemistry using anti-CD3 and F4/80 antibodies, respectively. Histologic glomerular damages were scored semi-quantitatively.

Results: The number of infiltrating T cells and monocytes and chemokine expressions in glomeruli of MLR/lpr mice significantly increased with age. Among the parameters examined, glomerular damage score was significantly correlated with number of monocytes, T-cells, and the expression level of glomerular CCL-2 (r=0.745, P=0.002; r=0.730, P<0.001; r=0.513, p=0.012, respectively). There was no correlation between damage score and CCL-5 or CXCL-10. Of note, number of infiltrating monocytes was highly correlated with glomerular CCL-2 (r=0.865, p<0.001).

Conclusion: Our data suggest that glomerular infiltrating T cells, monocytes and CCL-2 might have a potential role in glomerular damage of lupus-prone mice.

Page 73: APLAR 2016 Oral Abstracts

APL16-0727 Kinoid Vaccine of IL-17A Prevented Progressivity of Autoantibody Production in Pristane Induced Lupus Mice Model K. Handono1, D. Hasanah2, C.S. Wahono2, M. Zaka2, H. Kalim2 1Faculty of Medicine of Brawijaya University / Dr. Saiful Anwar General Hospital, Department of Clinical Pathology, Malang, Indonesia 2Faculty of Medicine of Brawijaya University / Dr. Saiful Anwar General Hospital, Rheumatology and Immunology Division Department of Internal Medicine, Malang, Indonesia

Background: Systemic lupus erythematosus (SLE) is a chronic systemic inflammatory autoimmune disease. We aimed to measure the effect of kinoid immunization against IL-17A on progressivity of SLE in pristane induced lupus mice model.

Methods: The subjects of this study were female Balb/c mice given with single 0.5 ml intraperitoneal injection of pristane to induce lupus manifestations. Kinoid vaccine used in this study was a mouse recombinant IL-17A, conjugated to keyhole limpet hemocyanin. Complete Freud's adjuvant was used in the first injection, while incomplete Freud's adjuvant was used in boosters. Mice were divided into three groups, based on the doses of the vaccines: control (no vaccine), G1 (1 μg/ml) and G2 (10 μg/ml). Vaccine was injected subcutaneously three times every two weeks. At the end of the study (day 42), anti-IL-17A-KLH complex titres, IL-17A and anti-dsDNA serum levels were measured by ELISA.

Results: Immunization with 10 μg/ml of IL-17A-KLH complex increased the titres of anti-IL-17A-KLH complex significantly (p: 0.027). The titres of anti-IL-17A-KLH complex were found increased significantly at day 21 and more increased at day 42 (p: 0.053 and 0.007, respectively). IL-17A serum levels also decreased significantly after injection of 10 μg/ml IL-17A-KLH complex (p < 0.001). Moreover, the injection of 10 μg/ml IL-17A-KLH complex could decrease the anti-dsDNA serum level (p: 0.021).

Conclusion: Active immunization with kinoid vaccine of IL-17A induced high titre of neutralizing antibody against IL-17 and decrease anti-dsDNA serum levels.

Page 74: APLAR 2016 Oral Abstracts

Systemic Sclerosis (SSc)

APL16-0231 A 18 month observation in patients with progressive systemic sclerosis treated with an intensified B-lymphocyte depletion -Clinical and immunological response D. Roccatello1, D. Rossi1 1University of Turin, Department of Clinical and Biological Science, Turin, Italy

B cells (BC) play a critical role in progressive systemic sclerosis (SS). BC depletion therapy is an attractive option. Eighteen patients with SS [2 males, mean age 58.33 yrs (46-82)] with severe multiorgan involvement including skin [16], lung, with pulmonary fibrosis (17 patients) and pulmonary hypertension (5), esophagous [9], with polyarthralgias [2] have been perspectively treated with an intensified B cell depletion therapy protocol due to their resistance or intolerance to previous therapy or as a front line treatment in noncompliant patients.

Patients were given Rituximab (RTX) 375mg/sm on days 1, 8, 15, 22, and 2 more doses after 1 and 2 months, associated with 2 IV administrations of 10mg/kg of cyclophosphamide and 3 methylprednisolone pulses (15mg/kg) followed by oral prednisone (0.8mg/kg/day, rapidly tapered to 5mg/day by the end of the 3rd month.

Patients had been followed-up for a mean of 21,67 ± ds 11,05 (06-43) months. Significant decreases (p<0.05) in Rodnan skin score (baseline: 12.28; end of follow-up: 11.67) and visual activity score (baseline: 6.8 mm; end of follow-up: 4.2) were found . Significant increases (p<0.05) in FVC (baseline: 92.35 ; end of follow-up: 95.44), FEV (baseline: 86.5; end of follow-up: 90.43), DLCO (baseline: 57.15; end of follow-up:66.75), and NTpro BNP (baseline: 345.19 ; end of follow-up: 62.29) were also observed. PAP values did not change during the observation (baseline:29.77mmHg; end of follow-up: 26.57).

Our data confirm the opportunity to consider the regimens of BL depletion in the treatment of the most severe or refractory forms of SS.

Page 75: APLAR 2016 Oral Abstracts

APL16-0453 Blocking Leukotriene B4/BLT1 Axis Prevents Myofibroblast Differentiation and Reliefs Skin and Lung Fibrosis in a Modified Systemic Sclerosis Mouse Model M. Liang1, J. Lv2, Y. Xiong2, R. He2, H. Zou1 1Institute of Rheumatology- Immunology and Allergy- Fudan University- Shanghai 200040- PR China., Division of Rheumatology- Huashan Hospital- Fudan University- Shanghai 200040- PR China., Shanghai, China 2School of Basic Medical Sciences- Fudan University- Shanghai- China, Department of Immunology, Shanghai, China

Leukotriene B4 (LTB4), a lipid mediator of inflammation, plays a key role in the autoimmune and inflammatory diseases via its high affinity receptor BLT1. Myofibroblast is recognized to be critical in the progression of systemic sclerosis (SSc), but the mechanism is still unknown. We aimed to use BLT1-/- mice and BLT1 specific inhibitor to reveal the contribution of LTB4/BLT1 axis to the progression of SSc in a modified SSc-interstitial lung disease (ILD) mouse model by delivering bleomycin (BLM) via an osmotic mini-pump.

In the present study, LTB4 was observed to be up-regulated in the plasma of SSc patients. Also, immunohistochemical analysis demonstrated overexpressions of BLT1 and leukotriene A4 hydrolase (LTA4H), the biosynthetic enzyme for LTB4, in both skin and lung tissues of SSc-ILD subjects. In addition, the levels of BLT1 and LTB4H were also increased in the skin and lung tissues of SSc-ILD mouse. BLT1-/- mice did not manifest the phenotype of SSc following the BLM treatment in the SSc-ILD mouse model. And the reduction of α-SMA+ myofibroblasts was also found in the skin and lung tissues of BLT1-/- mice following the administration of BLM, compared with those in wide type mice. Furthermore, the addition of LTB4 was observed to promote fibroblast-myofibroblast transition and adipocyte-myofibroblast transition in vitro using primary cell culture, which were reversed by BLT1 inhibition.

These results uncover a possible role for LTB4/BLT1 driven myofibroblast formation in SSc-ILD pathogenesis and identify a pathway that may be amenable to therapeutic targeting.

Page 76: APLAR 2016 Oral Abstracts

APL16-0544 Carotid Intima Media Thickness Is Increased In Patients of Systemic Sclerosis: Results from a Tertiary Centre, Cross Sectional, Case-Control Study S. sharma1, A. dhooria1, V. Dhir1, S. Singh1 1PGIMER, Dept of Internal Medicine, Chandigarh, India

Background: Atherosclerosis is a leading cause of morbidity and mortality in systemic sclerosis (SSc) 1. There is increasing evidence that atherosclerosis occurs prematurely in (SSc) 2-3.

Objective: The aim was to describe the parameters of subclinical vascular changes Carotid Intima Media Thickness (cIMT), Flow Mediated Dilatation (FMD), Ankle Brachial Pressure Index (ABPI)] in patients with SSc and compare with age and sex matched controls.

Methods: 50 patients of SSc aged 20-50 years were selected, compared with age and sex matched controls. Patients with diabetes, hypertension, dyslipidemia, smoking and thyroid disorders were excluded. cIMT was calculated using a linear probe (L 12-5 MHz) on a Philips iU 22 ultrasound machine at a distance of 2 cm from the carotid bulb. Endothelium-dependent FMD of brachial artery was expressed as percentage change in brachial artery diameter from baseline. ABPI of both lower limb was measured (using Doppler) and average value of ABPI was considered.

Results: cIMT was more in SSc patients as compared to controls (0.585 mm vs 0.571 mm; p=0.001). FMD in SSc patients were lower when compared to controls, (7.61% vs 8.03%; p=0.608). ABPI was similar in SSc patients and controls (1.056 vs 1.036; p= 0.398). cIMT did not show any correlation with age or duration of illness. ABPI showed significant inverse correlation with duration of illness (Rho= -0.385; p=0.006).

Conclusion: cIMT is increased in patients with systemic sclerosis as compared to matched controls and may serve as a useful marker for detection of subclinical atherosclerosis in these patients.

Page 77: APLAR 2016 Oral Abstracts

APL16-0701 Systemic Sclerosis causes clinically apparent hand arthritis which is associated with radiographic changes on high resolution US and MRI. S. Sharma1, A. Dhooria1, V. Dhir1, S. Singh1 1PGIMER, Dept of Internal Medicine, Chandigarh, India

Objectives: To determine prevalence of radiographic changes in wrist and hands of SSc patients having clinically apparent synovitis using ultrasound and MRI, and to correlate it with antibody subsets.i.e. Anti-Scl-70, Anti-centromere, Anti-U1-RNP, RF and Anti-CCP.

Methods: Patients meeting 1980 ACR criteria for systemic sclerosis and presenting with clinical synovitis were recruited. High Resolution Ultrasound and 3 T MRI were performed for joints of wrist and hand.

Results: 550 SSc patients were screened, 34 patients had clinical synovitis (68 hands) with a total of 1020 joints, 1740 bones were evaluated. All bones were evaluated for erosions (On Ultrasound and MRI) and edema (On MRI). Synovitis was seen in 65 (95.58%) hands on ultrasound and in 59 (86.76%) hands on MRI. Erosions were seen in 97% hands both on ultrasound and on MRI. Tenosynovitis was seen in 76.47% hands on ultrasound and in 77.94% hands on MRI. Bone edema was seen in 75% hands. Acro osteolysis was seen in 28 % of distal phalanges, MRI was more sensitive for the same. Bone edema was seen in significantly higher percentage of patients with DcSSc as compared to LcSSc(p<0.05). Other manifestations like synovitis, tenosynovitis, erosions and acro-osteolysis showed no significant correlation between disease subtype. Anti-bodies did not significantly affect the presence of synovitis, erosions, bone edema or tenosynovitis.

Conclusion: There is high prevalence of radiographic changes in bones and soft tissues of wrist and hand in Scleroderma, but synovitis, erosions, edema and tenosynovitis are of low grade.

Page 78: APLAR 2016 Oral Abstracts

Vasculitis

APL16-0316 The effect of Mycophenolate mofetil on treating Takayasu’s arteritis: experience of 33 Chinese patients J. Li1, X. Tian1, X. Zeng1 1Peking Union Medical College Hospital, Rheumatology and Clinical Immunology, Beijing, China

Background: In this study, we investigated the therapeutic effect of mycophenolate mofetil(MMF) on Chinese TAK patients by treating 33 TAK patients in out-patient clinics of PUMCH.

Methods: Thirty-three consecutive TAK outpatients were enrolled from 2014 to 2015 with consents. They were given MMF combined with corticosteroid. All patients were evaluated and followed-up every 3 months and vascular image studieswere repeated every 6 months. The effectiveness of MMF was defined as: (1) ESR < 20 mm/hr; (2) CRP < 10 mg/L or hs-CRP<3mg/L; (3) stable or improved in vascular image studies; (5) clinical assessment is stable, improved or in remission; (6) the dosage of corticosteroid could be tapered to less than 15mg/day (equivalent dosage of prednison). ESR < 40 mm/hr, CRP < 20 mg/L or hs-CRP < 6mg/L, but fulfilled for the other four criteria was defined as partial effective.

Results: MMF was effective in 15(45.6%) patients, including partial effective in one patient. Combined with methotrexate(MTX) less than 15mg/week, MMF was effective in 8(24.2%) patients, including partial effective in 3 patients. When combined with azathioprine(AZA) 100-150mg/day, MMF was effective in 3(9.1%) patients, including partial effective in one patients. Four patient withdraw due to side effect including gastrointestinal tract in 3 and HBV flare in one patient. Two patients failed to show effectiveness. MMF combined with tocilizumab and AZA was effective in one patient, who were partially responded to tocilizumab combining AZA therapy.

Conclusion: MMF alone, or combined with MTX or AZA, was effective in treatment of TAK. The overall effective rate was 78.9%.

Page 79: APLAR 2016 Oral Abstracts

APL16-0404 Giant Cell arteritis – an uncommon large vessel vasculitis in Asians? T. Barami1, J. Neale1, J. Burns2, A. Moorthy1 1University Hospitals of Leicester, Rheumatology Department, Leicester, United Kingdom 2University Hospitals of Leicester, Ophthalmology Department, Leicester, United Kingdom

Background: Giant cell arteritis (GCA) is a potentially sight threatening condition more common among Caucasians than South Asians. Leicester Hospitals in UK, serves as tertiary referral center with a large number of Asian population. Temporal artery biopsy (TAB) enable better diagnosis and management. We follow local Guidelines for TAB.

Objectives: To compare prevalence of GCA in Asian patients who underwent TAB as per local guidelines against Caucasian counterparts.

Methods: All patients who had TAB in 2015 were included and analysed retrospectively. The data collected from the two groups were compared and analyzed using SPSS and Microsoft Excel (2007).

Results: 71 biopsies were performed in the study period. 27% (n=19) were males and 73% (n=52) were females. 80% were Caucasians and 19% (n=14) were of Asians and one Afro-Caribbean ethnicity. Median age of Asians were 68 yrs . (63-82). 25% (n=18) patients had a positive biopsy. Out of 14 biopsies performed in those of Asian ethnicity, only one had a positive biopsy. Mean time for biopsy was 6.8 days (3-14).

Conclusions: Though clinical suspicion of GCA is low in Asian population, in our cohort,19% Asians underwent biopsy and only one was found to be positive. Asian patients with GCA symptoms need careful evaluation. Developing a scoring system using positive predictors - Age >65, female sex, jaw claudication, raised inflammatory markers, and ethnicity will enable better diagnosis in this ethnic group. We need a large prospective study among ethnic population for a better understanding.

Page 80: APLAR 2016 Oral Abstracts

APL16-0998 Clinical analysis of anti-neutrophil cytoplasmic antibody associated vasculitis combined with Interstitial lung disease X. Ronghua1 1Xijing Hospital- The Fourth Military Medical University, clinical Inmmune, Xi'an, China

Objective: To analyze the clinical manifestations, serology, chest CT, kidney pathological, treatment and prognosis of anti-neutrophil cytoplasmic antibody associated vasculitis (AVV) combined with Interstitial lung disease(ILD).

Method: Retrospective analysis of the data of AVV combined with (ILD) of Xijing Hospital from January 2008 to December 2015.

Results: There were 29 males and 29 female, with the mean age 61 years old, 52 Microscopic polyangiitis and 6 Granulomatosis with polyangiitis. The main symptoms were fever (63.80%), cough, sputum and dyspnea (60.34%) and myalgia and arthralgia (41.38%).The predominant manifest of chest CT is ILD (75.86%). Proteinuria (67.24%) and erythrocyturia (48.28%) were the main manifestations of kidney and the kidney pathology were crescent and fibrinoid necrosis. Others including weak (12.07%), conjunctival congestion (17.31%), edema (10.34%), numb (6.90%) and purpura (3.45%). All the patients were ANCA positive, 48 (82.76%) pANCA and myeloperoxidas positive, 10 (17.24%) cANCA and protease 3 positive.

Conclusion: AVV primarily affects the elder people. Besides kidney, lung is the main organ involved and respiratory failure is the predominant cause of death. The prognosis could be improved by treating with steroid and immunosuppressive agents.