Browsing by Author "Mukkada, Vincent"

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    Evaluating Eosinophilic Colitis as a Unique Disease Using Colonic Molecular Profiles: A Multi-Site Study
    (Elsevier, 2022) Shoda, Tetsuo; Collins, Margaret H.; Rochman, Mark; Wen, Ting; Caldwell, Julie M.; Mack, Lydia E.; Osswald, Garrett A.; Besse, John A.; Haberman, Yael; Aceves, Seema S.; Arva, Nicoleta C.; Capocelli, Kelley E.; Chehade, Mirna; Davis, Carla M.; Dellon, Evan S.; Falk, Gary W.; Gonsalves, Nirmala; Gupta, Sandeep K.; Hirano, Ikuo; Khoury, Paneez; Klion, Amy; Menard-Katcher, Calies; Leung, John; Mukkada, Vincent; Putnam, Philip E.; Spergel, Jonathan M.; Wechsler, Joshua B.; Yang, Guang-Yu; Furuta, Glenn T.; Denson, Lee A.; Rothenberg, Marc E.; Consortium of Eosinophilic Gastrointestinal Diseases Researchers (CEGIR); Pediatrics, School of Medicine
    Background & 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.