美国西奈山伊坎医学院Ephraim Kenigsberg、Judy H. Cho 和Miriam Merad等研究人员合作，利用单细胞测序技术鉴定到克罗恩病中存在一个病理性细胞单元与抗TNF治疗的耐药性相关。该项研究成果在线发表于2019年8月29日的《细胞》。
针对回肠克罗恩病（iCD）的细胞因子阻碍治疗仅使得一部分临床患者受益。研究人员将单细胞技术应用于iCD病变，以解决细胞异质性是否有助于治疗抵抗。研究人员发现一部分患者在炎症组织中存在一种独特的细胞单元，包括IgG浆细胞、炎症性单核吞噬细胞、活化T细胞和基质细胞，研究人员将其命名为GIMATS单元。配体-受体相互作用匹配分析确定了可能驱动GIMATS单元的独特网络连接。
引人注目的是，GIMATS单元也存在于四个独立的iCD队列研究中的一部分患者中（n = 441），并且其诊断到的存在与在抗TNF疗法的无效相关。
这些结果强调了当前诊断方式的局限性，以及单细胞测序在鉴定治疗反应中新的生物标志物和定制治疗方案方面的潜力。
附：英文原文
Title: Single-Cell Analysis of Crohn’s Disease Lesions Identifies a Pathogenic Cellular Module Associated with Resistance to Anti-TNF Therapy
Author: 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
Issue&Volume: 29 August 2019
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.
DOI: https://doi.org/10.1016/j.cell.2019.08.008
Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30896-7#