Precision Diagnosis and Differentiation of Eosinophilic Colitis and Inflammatory Bowel Disease Using a Tissue-Based Molecular Gene Expression Panel

BACKGROUND: Eosinophilic colitis (EoC) and eosinophil-predominant inflammatory bowel disease (IBD) can show overlapping clinical and histologic features, creating diagnostic uncertainty. Whether tissue gene expression can objectively distinguish these conditions in the setting of colonic eosinophilia remains unclear. OBJECTIVE: We sought to develop and validate a tissue-based molecular diagnostic panel to quantify eosinophilic inflammation and differentiate EoC from IBD-associated colonic eosinophilia. METHODS: This multi-center study analyzed 88 colonic biopsies from a cohort enriched for children and young adults, including 74 patients with EoC or IBD and non-disease controls. We developed a 96-gene qPCR-based platform, the Colonic Eosinophilia Diagnostic Panel (CEDP), and generated molecular EoC and IBD scores. Diagnostic accuracy was determined by area under the receiver operating characteristic curve (AUC). RESULTS: An EoC score developed from 59 genes (e.g., eosinophil-associated gene CLC) distinguished active EoC from non-disease controls (AUC 0.92, 95% CI 0.78-1.0) and quantified the active molecular eosinophilic inflammatory program, correlating with peak eosinophil counts. However, this score did not differentiate EoC from IBD. An IBD score from 18 genes (e.g., DUOXA2) reflecting inflammatory pathways provided complementary discriminatory information and resolved this overlap. This approach distinguished active IBD from all other groups (AUC 0.98, 95% CI 0.76-1.0) and specifically active EoC (AUC 0.99, 95% CI 0.95-1.0), correlated with endoscopic activity, and differentiated IBD with high colonic eosinophil counts. CONCLUSIONS: We developed the CEDP with a tissue-based, two-component molecular framework for evaluating colonic eosinophilia. By measuring eosinophilic inflammatory activity and identifying an IBD-associated molecular signature, this platform can distinguish EoC from IBD beyond conventional histopathology alone.