1. Evaluating Eosinophilic Colitis as a Unique Disease Using Colonic Molecular Profiles: A Multi-Site Study
- Author
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Tetsuo Shoda, Margaret H. Collins, Mark Rochman, Ting Wen, Julie M. Caldwell, Lydia E. Mack, Garrett A. Osswald, John A. Besse, Yael Haberman, Seema S. Aceves, Nicoleta C. Arva, Kelley E. Capocelli, Mirna Chehade, Carla M. Davis, Evan S. Dellon, Gary W. Falk, Nirmala Gonsalves, Sandeep K. Gupta, Ikuo Hirano, Paneez Khoury, Amy Klion, Calies Menard-Katcher, John Leung, Vincent A. Mukkada, Philip E. Putnam, Jonathan M. Spergel, Joshua B. Wechsler, Guang-Yu Yang, Glenn T. Furuta, Lee A. Denson, Marc E. Rothenberg, J. Pablo Abonia, Seema Aceves, Samuel Almonte, Rachel Andrews, Sara Anvari, Ashley Arrington, Nicoleta Arva, Fred Atkins, Dominique Bailey, Alexis Berry, Bridget Besl, Scott Bolton, Peter Bonis, Wendy Book, Kimberly Bray, Teresa Brown, Cassandra Burger, Deirdre Burke, Jonathon Cahoon, Kelley Capocelli, Eric Chiou, Margaret Collins, Carla Davis, Evan Dellon, Maureen DeMarshall, Lauren DiTommaso, Ranjan Dohil, Michael Eby, Gary Falk, David Fleischer, Heather Foote, Kelci Foss, Joel Friedlander, Patricia Fulkerson, Glenn Furuta, Debra Geno, Thomas Greuter, Sandeep Gupta, Frank Hamilton, Kirk Harris, Jennifer Harris, Girish Hiremath, Nicole Holland-Thomas, Lea Jacinto, Amir Kagalwalla, Timothy Kaseta, David Katzka, Kaitlin Keeley, Emad Khosh-Hemmat, Eileen King, Kara Kliewer, Jennifer Knowles, Kendra Kocher, Ellyn Kodroff, Jeffrey Krischer, Shay Kyle, Meredith Levy, Chris Liacouras, Denise Mack, Lisa Martin, Ellen Martin, Talaya McCright-Gill, Paul Menard-Katcher, Gabriela Mendoza, Melissa Mingler, Mike Minnicozzi, Amanda Muir, Vincent Mukkada, Cristin Murray-Petzold, Robert Newbury, Quan Nhu, Anthony Olive, Oghenekpaobor (Joel) Oyibo, Allisa Paliana, Zhaoxing Pan, Robbie Pesek, Kathryn Peterson, Heidi Poppendeck, Philip Putnam, Fabian Rivera, Marc Rothenberg, Amanda Rudman Spergel, Kathleen Sable, Alain Schoepfer, Melissa Scott, Rachel Sheridan, Selma Sinanovic, Jonathan Spergel, Mary Jo Strobel, Kiki Sun, Amy Tasco, Crystal Tholen, Katherine Thompson, Tiffany Tomkinson, Daisy Tran, Alexandra Tylicki, Tiina Urv, Mei-Lun Wang, Joshua Wechsler, Barry Wershil, Lisa Wheatley, Leah Wilkey, Angelika Zalewski, and Amy Zicarelli
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Colitis, Microscopic ,Hepatology ,Gastritis ,Eosinophilia ,Gastroenterology ,Humans ,Colitis ,Inflammatory Bowel Diseases ,Article ,Enteritis - Abstract
BACKGROUND AND 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 disease [CD, n=14]) were enrolled across sites associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). 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 < .001). Among EoC and other EGIDs, there was minimal transcriptomic overlap; and minimal evidence of a strong allergic type 2 immune response 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). CONCLUSION: 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.
- Published
- 2022