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.
journal_name
Celljournal_title
Cellauthors
Martin JC,Chang C,Boschetti G,Ungaro R,Giri M,Grout JA,Gettler K,Chuang LS,Nayar S,Greenstein AJ,Dubinsky M,Walker L,Leader A,Fine JS,Whitehurst CE,Mbow ML,Kugathasan S,Denson LA,Hyams JS,Friedman JR,Desai PT,Kodoi
10.1016/j.cell.2019.08.008subject
Has Abstractpub_date
2019-09-05 00:00:00pages
1493-1508.e20issue
6eissn
0092-8674issn
1097-4172pii
S0092-8674(19)30896-7journal_volume
178pub_type
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