创作:szx 审核:szx 2019年10月01日
  • 对回肠克罗恩病(iCD)患者的病灶进行单细胞测序,发现一部分患者的炎症组织中表现出一种独特的细胞模块——GIMATS;
  • 相比于正常组织,GIMATS模块中的IgG浆细胞、炎症性单核吞噬细胞、活化T细胞及基质细胞显著增加;
  • 在4个独立的iCD患者队列(共441名患者)中,部分患者的病灶中也存在GIMATS模块;
  • GIMATS模块的存在与抗TNF治疗的失败(未能完成持久的无需皮质类固醇的缓解)相关。
Cell [IF:38.637]

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



2019-09-05, Article

Abstract & Authors:展开

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.

First Authors:
Jerome C Martin

Correspondence Authors:
Miriam Merad,Judy H Cho,Ephraim Kenigsberg

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