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.