Abstract & Authors:展开
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.
Jerome C Martin
Miriam Merad,Judy H Cho,Ephraim Kenigsberg
Jerome C Martin,Christie Chang,Gilles Boschetti,Ryan Ungaro,Mamta Giri,John A Grout,Kyle Gettler,Ling-shiang Chuang,Shikha Nayar,Alexander J Greenstein,Marla Dubinsky,Laura Walker,Andrew Leader,Jay S Fine,Charles E Whitehurst,M Lamine Mbow,Subra Kugathasan,Lee A Denson,Jeffrey S Hyams,Joshua R Friedman,Prerak T Desai,Huaibin M Ko,Ilaria Laface,Guray Akturk,Eric E Schadt,Helene Salmon,Sacha Gnjatic,Adeeb H Rahman,Miriam Merad,Judy H Cho,Ephraim Kenigsberg