Eosinophil-Related Gene Expression in Children with Eosinophilic Gastrointestinal Disorders (EGIDs)

Rationale: Eosinophilic gastrointestinal disorders (EGIDs) are clinicopathologically characterized by massive eosinophilic infiltration into the GI tract and are classified into eosinophilic esophagitis (EoE), gastritis (EG), gastroenteritis (EGE) and colitis (EC) according to the site of infiltration. Studies revealed that eotaxin-3/CCL26 plays a crucial role in EoE, whereas the chemotactic factors associated with EGIDs remain obscure. In order to elucidate those factors, we investigated the expression of eosinophil-related genes in biopsy specimens from EGID (EG, EGE, EC) patients.

Methods: We obtained informed consent and then enrolled pediatric EGID patients, and also age-matched controls who underwent GI endoscopy due to clinical symptoms but had no eosinophilia (stomach, small intestine and colon; n=5 each). Eosinophilia in the GI mucosa was defined according to DeBrosse et al.’s report. The eosinophil-related gene expression profiles in the biopsies from each portion of the GI tract were determined.

Results: In agreement with the tissue eosinophilia of the patients, eosinophil-specific genes such as Charcot-Leyden crystals (CLC) and C-C chemokine receptor type 3 (CCR3) were significantly up-regulated (≥2 fold, p<0.05) in EG, EGE and EC patients compared with the controls. EG patients also showed markedly increased expression of mRNA for eotaxin-3/CCL26, MCP-3/CCL7 and IL-5RA compared with the controls. In EGE and EC patients, eotaxin-1/CCL11 was the most upregulated gene (≥5 fold, p<0.05).

Conclusions: Our results suggest that the main chemotactic factors inducing selective eosinophil recruitment differ with the portion of the GI tract: The main chemotactic factor for lower EGIDs was eotaxin-1/CCL11, whereas it was eotaxin-3/CCL26 for upper EGIDs.