Natural History Of Esophageal Remodeling In Pediatric Eosinophilic Esophagitis Treated For Four...
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986 Maternal Transfer Of Der p 1 and Blo t 5 Allergens and Their Respective Specific Antibodies Trough Placenta and Colostrum Dr. Patricia Macchiaverni 1 , Christina Arslanian 2 , Dr. Valerie Verhasselt 3 , Prof. Antonio Condino-Neto, MD, PhD 4 ; 1 Department of Immunology, Institute of Biomedical Sciences, University of S~ ao Paulo, SP, Brazil, 2 University of S~ ao Paulo, 3 INSERM, Valbonne, France, 4 Insti- tute of Biomedical Sciences, Department of Immunology, University of S~ ao Paulo, Sao Paulo, Brazil. RATIONALE: Dermatophagoides pteronyssinus (Der p) and Blomia tropicalis (Blo t) are respiratory allergens that represent a major cause of allergic asthma. Placental transfer and breastfeeding are potential routes of allergen exposure in very early life. To date, no study has demonstrated the presence of those respiratory allergens in paired samples of human cord blood and breast milk samples. METHODS: We assessed whether Der p 1 and Blo t 5 allergens and were transferred through placenta and colostrums in the presence of specific an- tibodies. The maternal transfer was analyzed in a cohort of 91 paired sam- ples of colostrum and umbilical cord blood. RESULTS: We detect Der p 1 and Blo t 5 in 29% and 9,6% of cord blood samples (median 62.2pg/mL and 892.4pg/ml, respectively). In colostrum 58.6% of samples were positive for Der p 1 and 41.3% for Blo t 5 (range 0- 869.9pg/mL and 0-1281pg/ml, respectively). Der p and Blo t-specific IgG1, IgG2, IgG3 and IgG4 were present in cord blood of almost all neo- nates in a wide range of values, but strongly correlated to maternal levels. More than 90% of cord blood samples were positive for specific IgM, for both allergens. In colostrums, specific IgA and IgG levels were also vari- able among samples. CONCLUSIONS: We demonstrated that respiratory allergen can be transferred trough placenta and colostrums and that the first actively stimulates the neonate immune system intra uterus. Those observations bring new hypothesis in understanding causal pathway of allergic airway sensitization and raise questions for future strategies for prevention of allergic disease. 987 Rhinovirus Infection Is Associated With Changes In The Airway Microbiome Dr. Kirsten Kloepfer, MD 1 , Dr. Valeriy Poroyko, PhD 2 , Mrs. Rose Vrtis, BS 3 , Mrs. Tressa Pappas, BS 3 , Dr. Theresa Kang, PhD 3 , Dr. Wai-Ming Lee, PhD 3 , Mr. Michael D. Evans, MS 3 , Dr. Ronald E. Gangnon, PhD 3 , Dr. Yury Bochkov, PhD 3 , Dr. Robert F. Lemanske, Jr, MD, FAAAAI 3 , Dr. James E. Gern, MD, FAAAAI 3 ; 1 Riley Hospital for Children at Indiana University Health, Indianapolis, IN, 2 University of Chicago, Chicago, IL, 3 University of Wisconsin School of Medicine and Public Health, Madison, WI. RATIONALE: Rhinovirus (RV) infection can cause a spectrum of illness from asymptomatic infection to moderate asthma exacerbations. Based on recent findings that the upper airway microbiome is altered in children with asthma, we examined the upper airway microbiome of children with asthma before and during RV infection to determine if changes occur and if they correlate with asthma exacerbation severity. METHODS: 30 children with asthma, ages 4-12 years, provided five consecutive weekly nasal samples during September and scored cold and asthma symptoms daily. We selected 15 subjects with asymptomatic RV- infection and 15 subjects with moderate asthma exacerbation associated with RV-infection. Bacterial DNAwas extracted from samples at baseline and during RVinfection. 16S-rRNA gene sequences targeting the v4 region were analyzed utilizing Mothur and Primer v6 software. RESULTS: 2,499 taxa were identified with 61 bacterial genera at 1% abundance level. 73% of annotated sequences consisted of Streptococcus (19%), Dolosigranulum (18%), Corinebacterium (14%), Staphylococcus (13%), and Moraxella (8%). RV infection was associated with increased abundance of Dolosigranulum, Corinebacterium, and Moraxella, while RV-negative samples were associated with increased abundance of Streptococcus, Staphylococcus, Gemella and Neisseria (p50.016). During RV infection, no difference was observed in microbiota composition between subjects with asymptomatic RV infection and those with RV-associated moderate asthma exacerbations (p50.33). CONCLUSIONS: RV infection causes changes in the upper airway microbiome; however, there were no significant differences in microbial community metrics related to asthma exacerbations. Further investigation is needed to determine if the baseline microbiome is different in children who experience moderate asthma exacerbations during RV infection. 988 Natural History Of Esophageal Remodeling In Pediatric Eosinophilic Esophagitis Treated For Four Years Dr. Jessica Rajan, MD 1,2 , Dr. Robert Newbury, MD 3,4 , Arjun Andrew Anilkumar, BS 2,5 , Ranjan Dohil, MD 6,7 , Dr. David H. Broide, MB, ChB, FAAAAI 8 , Seema Sharma Aceves, MD, PhD, FAAAAI 9 ; 1 Scripps Clinic Medical Group, San Diego, CA, 2 Division of Allergy/Immunology, 3 Department of Pediatrics, 4 Division of Pathology, 5 Department of Med- icine, 6 Department of Pediatrics, Division of Gastroenterology, 7 Division of Gastroenterology, UCSD, Rady Children’s Hospital, San Diego, 8 Department of Medicine, San Diego, CA, 9 Pediatrics, University of Cal- ifornia San Diego, La Jolla, CA. RATIONALE: Eosinophilic esophagitis (EoE) diagnosis and manage- ment requires repeated tissue procurement and provides a model system to study long-term eosinophil associated tissue remodeling. METHODS: We assessed 84 esophageal biopsies from 13 pediatric EoE subjects followed for an average of 45 months during routine clinical care. Tissue remodeling was quantitated using image analysis and standardized scoring tools. RESULTS: Baseline average epithelial eosinophil counts were 98613 per hpf, average time to recurrence of eosinophilia was 17.5 months and was associated with medication non-adherence or addition of an antigenic food. Control and recurrence of epithelial eosinophilia was associated with basal zone hyperplasia (r50.61, p<0.0001) and dilated intracellular space (r50.63, p<0.0001) severity. Forty-six biopsies had > _3 instances with evaluable lamina propria (LP). Initial responders to therapy had prolonged control (20.5 months) of fibrosis which was associated with decreased fibrosis scores (2.5 to 0.5, maximum53), epithelial eosinophils (6466 to 32621 per hpf,) LP eosinophils (16.5610.5 to 2.661.2 per hpf), and TGFb 1 -positive cells (18566206 to 14266190 per mm 3 ). Initial/pro- longed non-responders to therapy had persistent fibrosis (score53), in- creases in LP eosinophils (1165 to 2365 per hpf, p<0.05 compared with responders) and TGFb 1 -positive cells (11176190 to 18996311 per mm 3 ) over time (25.5 months). Non-responders had elevated TGFb 1 positive cells compared with non-EoE patients (p<0.03). CONCLUSIONS: Initial response to therapy may be associated with an ability to control remodeling while initial therapeutic non-response may predict persistent and/or progressive esophageal remodeling. J ALLERGY CLIN IMMUNOL FEBRUARY 2014 AB286 Abstracts TUESDAY
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Transcript of Natural History Of Esophageal Remodeling In Pediatric Eosinophilic Esophagitis Treated For Four...
J ALLERGY CLIN IMMUNOL
FEBRUARY 2014
AB286 Abstracts
TUESDAY
986 Maternal Transfer Of Der p 1 and Blo t 5 Allergens and TheirRespective Specific Antibodies Trough Placenta andColostrum
Dr. Patricia Macchiaverni1, Christina Arslanian2, Dr. Valerie
Verhasselt3, Prof. Antonio Condino-Neto, MD, PhD4; 1Department of
Immunology, Institute of Biomedical Sciences, University of S~ao Paulo,
SP, Brazil, 2University of S~ao Paulo, 3INSERM, Valbonne, France, 4Insti-
tute of Biomedical Sciences, Department of Immunology, University of
S~ao Paulo, Sao Paulo, Brazil.
RATIONALE: Dermatophagoides pteronyssinus (Der p) and Blomia
tropicalis (Blo t) are respiratory allergens that represent a major cause of
allergic asthma. Placental transfer and breastfeeding are potential routes of
allergen exposure in very early life. To date, no study has demonstrated the
presence of those respiratory allergens in paired samples of human cord
blood and breast milk samples.
METHODS: We assessed whether Der p 1 and Blo t 5 allergens and weretransferred through placenta and colostrums in the presence of specific an-
tibodies. The maternal transfer was analyzed in a cohort of 91 paired sam-
ples of colostrum and umbilical cord blood.
RESULTS: We detect Der p 1 and Blo t 5 in 29% and 9,6% of cord blood
samples (median 62.2pg/mL and 892.4pg/ml, respectively). In colostrum
58.6% of samples were positive forDer p 1 and 41.3% for Blo t 5 (range 0-
869.9pg/mL and 0-1281pg/ml, respectively). Der p and Blo t-specificIgG1, IgG2, IgG3 and IgG4 were present in cord blood of almost all neo-
nates in a wide range of values, but strongly correlated to maternal levels.
More than 90% of cord blood samples were positive for specific IgM, for
both allergens. In colostrums, specific IgA and IgG levels were also vari-
able among samples.
CONCLUSIONS: We demonstrated that respiratory allergen can be
transferred trough placenta and colostrums and that the first actively
stimulates the neonate immune system intra uterus. Those observations
bring new hypothesis in understanding causal pathway of allergic airway
sensitization and raise questions for future strategies for prevention of
allergic disease.
987 Rhinovirus Infection Is Associated With Changes In TheAirway Microbiome
Dr. Kirsten Kloepfer, MD1, Dr. Valeriy Poroyko, PhD2, Mrs. Rose
Vrtis, BS3, Mrs. Tressa Pappas, BS3, Dr. Theresa Kang, PhD3,
Dr. Wai-Ming Lee, PhD3, Mr. Michael D. Evans, MS3, Dr. Ronald E.
Gangnon, PhD3, Dr. Yury Bochkov, PhD3, Dr. Robert F. Lemanske, Jr,
MD, FAAAAI3, Dr. James E. Gern, MD, FAAAAI3; 1Riley Hospital for
Children at Indiana University Health, Indianapolis, IN, 2University of
Chicago, Chicago, IL, 3University of Wisconsin School of Medicine
and Public Health, Madison, WI.
RATIONALE: Rhinovirus (RV) infection can cause a spectrum of illness
from asymptomatic infection to moderate asthma exacerbations. Based on
recent findings that the upper airwaymicrobiome is altered in childrenwith
asthma, we examined the upper airway microbiome of children with
asthma before and during RV infection to determine if changes occur and if
they correlate with asthma exacerbation severity.
METHODS: 30 children with asthma, ages 4-12 years, provided five
consecutive weekly nasal samples during September and scored cold and
asthma symptoms daily. We selected 15 subjects with asymptomatic RV-
infection and 15 subjects with moderate asthma exacerbation associated
with RV-infection. Bacterial DNAwas extracted from samples at baseline
and during RVinfection. 16S-rRNA gene sequences targeting the v4 region
were analyzed utilizing Mothur and Primer v6 software.
RESULTS: 2,499 taxa were identified with 61 bacterial genera at 1%
abundance level. 73% of annotated sequences consisted of Streptococcus
(19%), Dolosigranulum (18%), Corinebacterium (14%), Staphylococcus(13%), and Moraxella (8%). RV infection was associated with increased
abundance of Dolosigranulum, Corinebacterium, and Moraxella, while
RV-negative samples were associated with increased abundance of
Streptococcus, Staphylococcus, Gemella and Neisseria (p50.016).
During RV infection, no difference was observed in microbiota
composition between subjects with asymptomatic RV infection and those
with RV-associated moderate asthma exacerbations (p50.33).
CONCLUSIONS: RV infection causes changes in the upper airway
microbiome; however, there were no significant differences in microbial
community metrics related to asthma exacerbations. Further investigation
is needed to determine if the baseline microbiome is different in children
who experience moderate asthma exacerbations during RV infection.
988 Natural History Of Esophageal Remodeling In PediatricEosinophilic Esophagitis Treated For Four Years
Dr. Jessica Rajan, MD1,2, Dr. Robert Newbury, MD3,4, Arjun Andrew
Anilkumar, BS2,5, Ranjan Dohil, MD6,7, Dr. David H. Broide, MB,
ChB, FAAAAI8, Seema Sharma Aceves, MD, PhD, FAAAAI9; 1Scripps
Clinic Medical Group, San Diego, CA, 2Division of Allergy/Immunology,3Department of Pediatrics, 4Division of Pathology, 5Department of Med-
icine, 6Department of Pediatrics, Division of Gastroenterology, 7Division
of Gastroenterology, UCSD, Rady Children’s Hospital, San Diego,8Department of Medicine, San Diego, CA, 9Pediatrics, University of Cal-
ifornia San Diego, La Jolla, CA.
RATIONALE: Eosinophilic esophagitis (EoE) diagnosis and manage-
ment requires repeated tissue procurement and provides a model system to
study long-term eosinophil associated tissue remodeling.
METHODS: We assessed 84 esophageal biopsies from 13 pediatric EoE
subjects followed for an average of 45 months during routine clinical care.
Tissue remodeling was quantitated using image analysis and standardized
scoring tools.
RESULTS: Baseline average epithelial eosinophil counts were 98613 per
hpf, average time to recurrence of eosinophilia was 17.5 months and was
associatedwithmedication non-adherence or addition of an antigenic food.
Control and recurrence of epithelial eosinophilia was associated with basal
zone hyperplasia (r50.61, p<0.0001) and dilated intracellular space
(r50.63, p<0.0001) severity. Forty-six biopsies had >_3 instances with
evaluable lamina propria (LP). Initial responders to therapy had prolonged
control (20.5 months) of fibrosis which was associated with decreased
fibrosis scores (2.5 to 0.5, maximum53), epithelial eosinophils (6466 to
32621 per hpf,) LP eosinophils (16.5610.5 to 2.661.2 per hpf), and
TGFb1-positive cells (18566206 to 14266190 per mm3). Initial/pro-
longed non-responders to therapy had persistent fibrosis (score53), in-
creases in LP eosinophils (1165 to 2365 per hpf, p<0.05 compared
with responders) and TGFb1-positive cells (11176190 to 18996311 per
mm3) over time (25.5 months). Non-responders had elevated
TGFb1positive cells compared with non-EoE patients (p<0.03).CONCLUSIONS: Initial response to therapy may be associated with an
ability to control remodeling while initial therapeutic non-response may
predict persistent and/or progressive esophageal remodeling.
