GSE134809
Single-cell analysis of Crohn's disease lesions identifies a pathogenic cellular module associated with resistance to anti-TNF therapy
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 connectivity network that likely drives the GIMATS module. Strikingly, the GIMATS module was also present in a subset of patients in 4 independent iCD cohorts (n=441), and its presence at diagnosis correlated with failure to achieve corticosteroid-free durable 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 Overall design: Single cell seq analysis of paired resection ileal samples from inflamed and uninflamed area