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Single-Cell Analysis of Crohn’s Disease Lesions Identifies a Pathogenic Cellular Module Associated with Resistance to Anti-TNF Therapy

Open access
Martin, Jerome C., Chang, Christie, Boschetti, Gilles, Ungaro, Ryan, Giri, Mamta, Grout, John A., Gettler, Kyle, Chuang, Ling-shiang, Nayar, Shikha, Greenstein, Alexander J., Dubinsky, Marla, Walker, Laura, Leader, Andrew, Fine, Jay S., Whitehurst, Charles E., Mbow, M Lamine, Kugathasan, Subra, Denson, Lee A., Hyams, Jeffrey S., Friedman, Joshua R., Desai, Prerak T., Ko, Huaibin M., Laface, Ilaria, Akturk, Guray, Schadt, Eric E., Salmon, Helene, Gnjatic, Sacha, Rahman, Adeeb H., Merad, Miriam, Cho, Judy H., Kenigsberg, Ephraim·2019·Cell

Abstract

SUMMARY 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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Metadata

Authors
Martin, J. C., Chang, C., Boschetti, G., Ungaro, R., Giri, M., Grout, J. A., Gettler, K., Chuang, L.-S., Nayar, S., Greenstein, A. J., Dubinsky, M., Walker, L., Leader, A., Fine, J. S., Whitehurst, C. E., Mbow, M. L., Kugathasan, S., Denson, L. A., Hyams, J. S., Friedman, J. R., Desai, P. T., Ko, H. M., Laface, I., Akturk, G., Schadt, E. E., Salmon, H., Gnjatic, S., Rahman, A. H., Merad, M., Cho, J. H., & Kenigsberg, E.
Venue
Cell
Publisher
Elsevier BV
Published
2019-09
Volume
178
Issue
6
Pages
1493-1508.e20
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2970463661
Cited by
872
References
104
FWCI
46.05
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Single-Cell Analysis of Crohn’s Disease Lesions Identifies a Pathogenic Cellular Module Associated with Resistance to Anti-TNF Therapy. https://app.cochat.ai/papers/10.1016/j.cell.2019.08.008
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Martin, J. C., Chang, C., Boschetti, G., Ungaro, R., Giri, M., Grout, J. A., Gettler, K., Chuang, L.-S., Nayar, S., Greenstein, A. J., Dubinsky, M., Walker, L., Leader, A., Fine, J. S., Whitehurst, C. E., Mbow, M. L., Kugathasan, S., Denson, L. A., Hyams, J. S., . . . Kenigsberg, E. (2019). Single-Cell Analysis of Crohn’s Disease Lesions Identifies a Pathogenic Cellular Module Associated with Resistance to Anti-TNF Therapy. Cell. https://doi.org/10.1016/j.cell.2019.08.008

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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