| Literature DB >> 31474370 |
Jerome C Martin1, Christie Chang1, Gilles Boschetti1, Ryan Ungaro2, Mamta Giri3, John A Grout1, Kyle Gettler3, Ling-Shiang Chuang3, Shikha Nayar3, Alexander J Greenstein4, Marla Dubinsky5, Laura Walker6, Andrew Leader1, Jay S Fine7, Charles E Whitehurst7, M Lamine Mbow7, Subra Kugathasan8, Lee A Denson9, Jeffrey S Hyams10, Joshua R Friedman11, Prerak T Desai11, Huaibin M Ko12, Ilaria Laface13, Guray Akturk13, Eric E Schadt14, Helene Salmon1, Sacha Gnjatic15, Adeeb H Rahman16, Miriam Merad17, Judy H Cho18, Ephraim Kenigsberg19.
Abstract
Clinical benefits of cytokine blockade in ileal Crohn's disease (iCD) are limited to a subset of patients. Here, we applied single-cell technologies to iCD lesions to address whether cellular heterogeneity contributes to treatment resistance. We found that a subset of patients expressed a unique cellular module in inflamed tissues that consisted of IgG plasma cells, inflammatory mononuclear phagocytes, activated T cells, and stromal cells, which we named the GIMATS module. Analysis of ligand-receptor interaction pairs identified a distinct network connectivity that likely drives the GIMATS module. Strikingly, the GIMATS module was also present in a subset of patients in four independent iCD cohorts (n = 441), and its presence at diagnosis correlated with failure to achieve durable corticosteroid-free remission upon anti-TNF therapy. These results emphasize the limitations of current diagnostic assays and the potential for single-cell mapping tools to identify novel biomarkers of treatment response and tailored therapeutic opportunities.Entities:
Keywords: Crohn’s disease; high-dimensional profiling; inflammatory bowel disease; molecular classification; single-cell RNA sequencing
Year: 2019 PMID： 31474370 PMCID： PMC7060942 DOI： 10.1016/j.cell.2019.08.008
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582