Wednesday, 14 October 2015: 16:45 - 17:00
Room R1 ABC (Floor 3) (Coex Convention Center)
Tetsuo Shoda
,
National Center for Child Health and Development, Tokyo, Japan
Akio Matsuda
,
National Research Institute for Child Health & Development, Tokyo, Japan
Katsuhiro Arai
,
National Center for Child Health and Development, Tokyo, Japan
Hirotaka Shimizu
,
National Center for Child Health and Development, Tokyo, Japan
Hideaki Morita, MD, PhD
,
National Research Institute for Child Health & Development, Tokyo, Japan
Naoko Okada
,
National Research Institute for Child Health & Development, Tokyo, Japan
Kanami Orihara
,
National Research Institute for Child Health & Development, Tokyo, Japan
Masami Narita
,
National Center for Child Health and Development, Tokyo, Japan
Yukihiro Ohya
,
National Center for Child Health and Development, Tokyo, Japan
Hirohisa Saito, MD, PhD
,
National Research Institute for Child Health & Development, Tokyo, Japan
Kenji Matsumoto
,
National Research Institute for Child Health & Development, Tokyo, Japan
Ichiro Nomura
,
National Center for Child Health and Development, Tokyo, Japan
Background: Eosinophilic gastroenteritis (EGE) is a gastrointestinal (GI) inflammatory disorder characterized by massive infiltration of eosinophils into the intestinal wall. Infantile EGE often manifests non-specific GI symptoms such as profound weight loss, and it thus remains difficult to diagnose. Moreover, repeated GI endoscopy, even though required for proper diagnosis, is extremely invasive for small infants. Availability of blood biomarkers would greatly facilitate diagnosis of infantile EGE. To find clinically useful biomarkers of EGE in children, we investigated the cytokine secretion profiles in the sera of patients with EGE and mRNA expression in intestinal tissue specimens.
Methods: Infantile EGE patients and clinically relevant controls were recruited after obtaining informed consent from their guardians. The cytokine profiles (10 infantile EGE patients and 83 controls) were analyzed using a Milliplex assay system. mRNA expression of the biopsy specimen (5 EGE patients, 5 ulcerative colitis patients and 5 age-matched controls) were assessed by microarray (Agilent Technology) and qPCR analysis.
Results: Among the 36 analyzed serum cytokines/chemokines, thymic stromal lymphopoietin (TSLP), IL33, CCL7/MCP3 and CCL21/6CKine were specifically increased in EGE. The diagnostic usefulness of these serum cytokines/chemokines was investigated by setting their cut-off points at the optimal points, and only TSLP and IL33 showed profound sensitivity (70.0%) and specificity (TSLP, 97.6%; IL33, 95.2%) for EGE. In addition, a strong positive correlation (r = 0.9) was seen between the concentrations of TSLP and IL33. The concentrations of TSLP and IL33 correlated with disease activity and decreased when the symptoms were improved by elimination of milk from the diet. In agreement with the serum findings, the microarray and qPCR results also showed significantly increased expression of TSLP and IL33 in the GI mucosa of EGE.
Conclusions: We found that both serum TSLP and IL33 were specifically elevated in infantile EGE, and we also demonstrated their up-regulation in the GI mucosa. TSLP and IL33 may play critical roles in the pathogenesis of EGE through inducing and/or amplifying Th2-type inflammation. The roles of these cytokines may provide novel therapeutic targets and/or candidates for useful diagnostic tests for EGE.
