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philic inflammation in esophageal epithelium in EoE. TCS can also diminish
PhD2, Masami Narita, MD, PhD2, Yukihiro Ohya, MD, PhD2, Hirohisa
subepithelial fibrosis pediatric EoE subjects who respond to therapy. However,
Saito, MD, PhD, FAAAAI1, and Kenji Matsumoto, MD, PhD1; 1National
whether topical steroids direct alter esophageal fibroblast function and whether
Research Institute for Child Health and Development, Tokyo, Japan, 2Na-
there are differential effects on normal versus EoE fibroblasts is unclear.
tional Center for Child Health and Development, Tokyo, Japan.
METHODS: Esophageal fibroblasts from 3 children with active EoE (2
RATIONALE: Eosinophilic gastroenteritis (EGE) is characterized by
non-responders to budesonide, 1 on proton pump inhibitor monotherapy)
abnormal accumulation of eosinophils in the GI mucosa. Non-IgE-
and 2 healthy donors were isolated and cultured from the esophagus. EoE
mediated immune responses are reportedly involved in the pathogenesis
and normal fibroblasts were matched for culture conditions and passage
of infantile EGE, but the pathogenesis of EGE remains largely unknown.
and treated concurrently. Fibroblasts were treated with TGFb1 (1ng/ml) in
One of the major difficulties in diagnosing and treating EGE is the lack of
the presence or absence of budesonide (0.01uM) and qPCR was performed
reliable serum biomarkers. We recently reported that serum TSLP, IL-33,
to analyze gene expression of fibrotic genes.
6Ckine and MCP-3 levels were elevated in infantile EGE (Shoda et al.,
RESULTS: Both EoE and normal fibroblasts had significant increases in
JACI 2016). In the present study, we examined the serum cytokine/
remodeling gene expression with TGFb1 treatment (collagen, fibronectin, PLN,
chemokine profiles of school age and adult patients with EGE.
PAI-1, and aSMA p<0.01 for all). Both EoE and normal fibroblasts had
METHODS: We used a Milliplex assay system to determine the
significant decreases in TGFb1-induced collagen and PLN (p<0.01) in the
comprehensive cytokine/chemokine profiles in sera from 9 patients with
presence of budesonide but only normal fibroblasts had a significant reduction in
moderate to severe EGE, 14 patients with ulcerative colitis (UC) and 31
TGFb1 induced aSMA (p<0.001). Compared with normal fibroblasts, EoE
patients with immediate-type food allergy (FA).
fibroblasts had significantly less down regulation of TGFb1-induced fibronectin,
RESULTS: The EGE patients were 3 males and 6 females, with a median
aSMA, PLN, and PAI-1 expression in the presence of budesonide (p<0.01 for all).
age of 12 years (5;35 y). Major symptoms and signs of EGE were
CONCLUSIONS: Budesonide was less effective at inhibiting fibrotic
abdominal pain (100%), vomiting (33%), diarrhea (56%), ascites (22%)
genes expression in EoE as opposed to normal fibroblasts. This may reflect
and hypoproteinemia (33%). Among 66 chemokines/cytokines tested,
intrinsic differences in esophageal fibroblasts from diseased versus normal
TSLP (P5.035), IL-33 (P<.000), 6CKine (P5.003) and MCP3 (P5.008)
subjects and may have therapeutic implications in EoE.
levels were elevated in EGE when compared with UC and FA. Those
elevated levels decreased after resolution of the symptoms. Serum
434 Daily Yogurt Consumption In Infancy Is Associated
With Reduced Skin Hypersensitivity proinflammatory cytokine levels were not elevated.
CONCLUSIONS: Serum TSLP, IL33, 6CKine, MCP3 levels are likely to
Miwa Shinohara, MD, PhD1, and Kenji Matsumoto, MD, PhD2; be good biomarkers for diagnosing and treating school children and older
1
Department of Pediatrics, Ehime University Hospital, Toon, Japan; patients with EGE. EGE in school children and older patients may have a
similar pathogenesis with infantile EGE.
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