Shoda, TetsuoCollins, Margaret H.Rochman, MarkWen, TingCaldwell, Julie M.Mack, Lydia E.Osswald, Garrett A.Besse, John A.Haberman, YaelAceves, Seema S.Arva, Nicoleta C.Capocelli, Kelley E.Chehade, MirnaDavis, Carla M.Dellon, Evan S.Falk, Gary W.Gonsalves, NirmalaGupta, Sandeep K.Hirano, IkuoKhoury, PaneezKlion, AmyMenard-Katcher, CaliesLeung, JohnMukkada, VincentPutnam, Philip E.Spergel, Jonathan M.Wechsler, Joshua B.Yang, Guang-YuFuruta, Glenn T.Denson, Lee A.Rothenberg, Marc E.Consortium of Eosinophilic Gastrointestinal Diseases Researchers (CEGIR)2024-05-072024-05-072022Shoda T, Collins MH, Rochman M, et al. Evaluating Eosinophilic Colitis as a Unique Disease Using Colonic Molecular Profiles: A Multi-Site Study. Gastroenterology. 2022;162(6):1635-1649. doi:10.1053/j.gastro.2022.01.022https://hdl.handle.net/1805/40519Background & aims: Colonic eosinophilia, an enigmatic finding often referred to as eosinophilic colitis (EoC), is a poorly understood condition. Whether EoC is a distinct disease or a colonic manifestation of eosinophilic gastrointestinal diseases (EGIDs) or inflammatory bowel disease (IBD) is undetermined. Methods: Subjects with EoC (n = 27) and controls (normal [NL, n = 20], Crohn's disease [CD, n = 14]) were enrolled across sites associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers. EoC was diagnosed as colonic eosinophilia (ascending ≥100, descending ≥85, sigmoid ≥65 eosinophils/high-power field) with related symptoms. Colon biopsies were subjected to RNA sequencing. Associations between gene expression and histologic features were analyzed with Spearman correlation; operational pathways and cellular constituents were computationally derived. Results: We identified 987 differentially expressed genes (EoC transcriptome) between EoC and NL (>1.5-fold change, P < .05). Colonic eosinophil count correlated with 31% of EoC transcriptome, most notably with CCL11 and CLC (r = 0.78 and 0.77, P < .0001). Among EoC and other EGIDs, there was minimal transcriptomic overlap and minimal evidence of a strong allergic type 2 immune response in EoC compared with other EGIDs. Decreased cell cycle and increased apoptosis in EoC compared with NL were identified by functional enrichment analysis and immunostaining using Ki-67 and cleaved caspase-3. Pericryptal circumferential eosinophil collars were associated with the EoC transcriptome (P < .001). EoC transcriptome-based scores were reversible with disease remission and differentiated EoC from IBD, even after controlling for colonic eosinophil levels (P < .0001). Conclusions: We established EoC transcriptomic profiles, identified mechanistic pathways, and integrated findings with parallel IBD and EGID data. These findings establish EoC as a distinct disease compared with other EGIDs and IBD, thereby providing a basis for improving diagnosis and treatment.en-USPublisher PolicyColitisEosinophilEosinophilic colitisInflammatory bowel diseaseTranscriptomeArticle