Article Synopsis
- Cytokine blockade therapies for ileal Crohn's disease only benefit certain patients, prompting a study on cellular differences in inflamed tissues.
- Researchers identified a unique group of immune cells in a subset of patients, termed the GIMATS module, which may contribute to resistance against treatment.
- The presence of the GIMATS module was confirmed in multiple patient groups and linked to poor outcomes with anti-TNF therapy, highlighting the need for better diagnostic methods and new ways to personalize treatment.
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Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060942 | PMC |
| http://dx.doi.org/10.1016/j.cell.2019.08.008 | DOI Listing |
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