The DOI matches its Crossref record; 104 of the 104 references it cites were found in a registry or an index.
Single-Cell Analysis of Crohn’s Disease Lesions Identifies a Pathogenic Cellular Module Associated with Resistance to Anti-TNF Therapy
Open accessAbstract
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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- 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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