J ALLERGY CLIN IMMUNOL

VOLUME 133, NUMBER 2

Abstracts AB257

ESDAY

887 Older Mice Intranasally Sensitized with AspergillusFumigatus Develop Stronger Eosinophilic EsophagealInflammation Compared to Their Younger Counterparts

Dr. Antonella Cianferoni, MD, PhD1, Simona Barni, MD2, Cara

Smith, BS3, Valsamma Abraham, PhD4, Peng Guan, BS3, Dr. Francesca

Saretta, MD5, Katie Ruyman, BS3, Hamid Bassiri, MD, PhD3, Dr. Kim

E. Nichols, MD6, Dr. Jonathan M. Spergel, MD, PhD, FAAAAI3,7; 1The

Children’s Hospital of Philadelphia, 2University of Florence Italy, Italy,3Children’s Hospital of Philadelphia, 4University of Pennsylvania, 5Ospe-

dale Di Palmanova, ASS 5 Bassa Friulana, Pagnacco, Italy, 6Children’s

Hospital of Philadelphia, Philadelphia, PA, 7The Children’s Hospital of

Philadelphia, Philadelphia, PA.

RATIONALE: Eosinophilic esophagitis (EoE) is characterized by

esophageal eosinophilia (EsoEo) and Th2 inflammation. Manifestations

of active inflammation occur in children, whereas those of chronic

inflammation are common in adults. We used an EoE mouse model to

define how age may influence inflammation in EoE.

METHODS: Three groups (n510) of different age BALB/cmice YM56-

8 weeks. MM512-14 weeks, and OM520-22 weeks were intranasally

sensitized with 100 mg of Aspergillus fumigatus or control saline 3 times a

week. After 4 weeks esophageal tissue was immunostained for EsoEo

using anti- major basic protein. Lymphocytes from gut and liver were

analyzed by flow-cytometry for invariant natural killer T cell (iNKTs) and

T regulatory cells (Treg). Institutional IACUC approved the study. ANOVA

was used for statistical analysis. P <0.05 was considered statistically

significant.

RESULTS: Sensitized OM compared to YM and MM had:1) higher

EsoEo (mean 6SD5 59.263.1;21.26 5.5;1565.15) (p50.0103); lower

percentages (%) and absolute numbers (#) of iNKTs in the gut (0.460.2

;1.661.5; 3.4610) (p50.003) and in the liver (2.361.1 , 43.1626.3;

29.4619.7) (p50.001); higher % and # of Treg in the gut (3.6 65.4;0.06

60.06 ; 1.961.6 ) (p50.0002) and lower in the liver (0.8 6 1.1;16

615.9 , 4.363.6 ) (p50.004) and data not shown.

CONCLUSIONS: OM compared to their younger counterparts, showed

more severe EsoEo associated with different levels iNKTs and Treg

Older mice may have different immune regulatory responses that favor a

more severe eosinophilia. Differences in immunological responses to

allergens may explain the different clinical picture observed in adult and

children.

888 Cripto-1 Is Elevated In Pediatric Subjects With EosinophilicEsophagitis

Lisa Beppu, BS1, Arjun Andrew Anilkumar, BS2, Richard Kurten, PhD3,

Ranjan Dohil, MD4, David Broide, MB ChB2, Seema Sharma Aceves,

MD, PhD, FAAAAI5; 1University of California San Diego, Department

of Pediatrics, Division of Allergy and Immunology, 2University of Cali-

fornia San Diego, Department of Medicine, Division of Allergy and

Immunology, 3University of Arkansas for Medical Sciences, Little

Rock, AR, 4University of California San Diego, Rady Children’s Hospital,

Department of Pediatrics, Division of Gastroenterology, 5Pediatrics, Uni-

versity of California San Diego, La Jolla, CA.

RATIONALE: Eosinophilic esophagitis (EoE) is a chronic antigen

mediated allergic response leading to tissue remodeling that includes

basal zone hyperplasia and fibrosis in both pediatric and adult patients.

Cripto-1, a member of the CFC-EGF family, is known to induce epithelial

tomesenchymal transition (EMT) and epithelial cell proliferation. The role

of Cripto-1 in EoE has yet to be characterized.

METHODS: Immunohistochemistry and qPCR were utilized to quanti-

tate Cripto-1 and its receptor, Glypican-1, in biopsies and cultured primary

esophageal epithelial cells from pediatric EoE and non-diseased control

subjects.

RESULTS: Immunohistochemistry and quantitative image analysis

using a Cripto-1 specific antibody on paraffin-embedded specimens

from active EoE subjects (n5 43) and non-diseased controls (n5 6)

U

demonstrated elevated Cripto-1 in the epithelium of EoE patients

compared to normal (p5 0.0005). Elevated Cripto-1 in the epithelium

correlated with epithelial basal zone hyperplasia (rs50.80, p5 0.0001). In

addition, immunohistochemistry and quantitative PCR confirmed the

presence of the Cripto-1 receptor, Glypican-1, in both paraffin-embedded

specimens and cultured primary esophageal epithelial cells from EoE

patients.

CONCLUSIONS: Pediatric EoE subjects have elevated epithelial Cripto-

1 compared to control whichmay allude to amechanistic pathway in which

the signaling molecule binds to its receptor, Glypican-1, and has

downstream effects contributing to tissue remodeling.

889 Interleukin-33 and Thymic Stromal Lymphopoietin ArePreferentially Elevated In The Sera Of Infants WithEosinophilic Gastroenteritis

Dr. Ichiro Nomura, MD, PhD1,2, Dr. Akio Matsuda, PhD2, Dr. Tetsuo

Shoda, MD2, Dr. Hideaki Morita, MD, PhD2, Dr. Katsuhiro Arai, MD3,

Dr. Hirotaka Shimizu, MD3, Dr. Yoshiyuki Yamada, MD, PhD4,

Dr. Yukihiro Ohya, MD, PhD1, Dr. Hirohisa Saito, MD, PhD2, Dr. Kenji

Matsumoto, MD, PhD2; 1Division of Allergy, National Center for Child

Health and Development, Tokyo, Japan, 2Department of Allergy and

Immunology, National Research Institute for Child Health and Develop-

ment, Tokyo, Japan, 3Division of Gastroenterology, National Center for

Child Health and Development, Tokyo, Japan, 4Gunma Children’s Medi-

cal Center, Shibukawa, Japan.

RATIONALE: Eosinophilic gastroenteritis (EGE) is a rare gastrointes-

tinal inflammatory disorder characterized by massive infiltration of

eosinophils in intestinal biopsy specimens. The pathogenesis of EGE

remains largely unsolved. However, we recently experienced infants and

young children with EGE whose symptoms improved after elimination of

Cow’s milk and/ or other allergens from their diet. Hoping to elucidate the

pathogenesis of EGE in children, we investigated the cytokine profiles of

their sera.

METHODS: Sera were obtained from 17 infants and young children

with EGE (15 boys and 2 girls; median age, 8 months; range, 4 to 36

months) after obtaining informed consent from their guardians. As

controls, sera were also obtained from 33 child patients with

atopic dermatitis (AD) without EGE and 45 healthy age-matched

children. Cytokine profiles were determined using a Milliplex assay

system.

RESULTS: IL33 and thymic stromal lymphopoietin (TSLP) were

significantly elevated in the patients with EGE, compared with both

control groups. The concentrations of IL33 and TSLP correlated with

disease activity. In addition, a strong positive correlation (r 5 0.87) was

seen between the concentrations of IL33 and TSLP, whereas IL-33

showed no correlation with either IL-13 or IL-5. IL33 and TSLP

decreased and the symptoms were improved by elimination of food

allergens from the diet.

CONCLUSIONS: IL33 and TSLP likely play critical roles in the

pathogenesis of EGE. The mechanisms of induction of both of these

cytokines, or these cytokines themselves, may be novel therapeutic targets

for EGE.

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