Coexisting Th1 and Th2 cytokines in patients with collagenous gastritis and implications for its pathogenesis

ObjectivesCollagenous gastritis (CG) is a rare cause of refractory dyspepsia and anemia that frequently affects children and young adults and whose histological hallmark is chronic mucosal inflammation with a subepithelial collagen band. The etiology remains obscure, and no established treatments exist. We investigated the pathogenesis of CG by determining the expression profiles of genes related to immunity and inflammation in index biopsies.MethodsGastric biopsies from 10 newly diagnosed patients with CG were evaluated using the NanoString nCounter assay. Gastric biopsies from 14 normal individuals served as controls. The gene expression ratios for CG versus controls were determined in pooled samples and confirmed in individual samples by quantitative reverse transcription polymerase chain reaction. The results were compared with previously reported expression data from a cohort of patients with collagenous colitis, a colonic disorder with similar morphology, including subepithelial collagen band.ResultsCG biopsies featured enhanced expression of key genes encoding both Th1 (IFN gamma, TNF-alpha, IL-2, IL-10, IL-12A, IL-12B, and IL-18) and Th2 cytokines (IL-3, IL-4, IL-5, IL-6, and IL-13). In contrast, biopsies from patients with CC exhibited upregulated Th1 cytokines only.ConclusionsWe show in this first published gene expression profiling study that CG involves simultaneous upregulation of Th1 and Th2 cytokines. This finding is unique, contrasting with other types of chronic gastritis as well as with collagenous colitis, which shares the presence of a collagen band. Involvement of Th2 immunity in CG would support further investigation of potential dietary, environmental, or allergic factors to guide future therapeutic trials. image Gene expression profiling of mucosal biopsies from affected patients revealed enhanced co-expression of Th1 and Th2 cytokines. Coexpression of Th1 and Th2 immunity is generally uncommon and distinguishes CG from other types of chronic gastritis as well as from collagenous colitis, which has a similar collagen band. The presence of enhanced Th2 cytokine expression in CG suggests an abnormal immune response to environmental factors, for example, foods, allergens, or other unknown triggers, and might serve to guide future therapeutic trials.What is Known? Collagenous gastritis (CG) is a rare chronic gastritis of unknown pathogenesis that features a distinctive subepithelial collagen band and manifests with refractory anemia and dyspepsia. The etiology of collagenous gastritis remains obscure, and no established treatments exist.