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单细胞转录组分析指导药物过敏综合征的靶向治疗
2020-01-25 10:42
来源：小柯机器人

美国国立健康研究院Keisuke Nagao研究团队报道了一个利用单细胞转录组学分析靶向治疗药物性过敏反应综合征的临床案例。相关论文2020年1月20日在线发表在《自然—医学》上。

研究人员表示，具有嗜酸性粒细胞增多和全身症状（DiHS/DRESS）的药物诱发超敏综合症/药物反应是与疱疹病毒再激活及随后自身免疫疾病发作相关的潜在致命多器官炎性疾病。由于其病理生理学仍然难以捉摸，治疗选择有限。皮质类固醇激素治疗难治的病例变成临床难题，大约30％的DiHS/DRESS患者会发生并发症，包括感染以及炎性和自身免疫性疾病。单细胞RNA测序（scRNA-seq）的进展提供了以前所未有的分辨率剖析人类疾病病理生理学的机会，特别是在缺乏动物模型的疾病（例如DiHS / DRESS）中。
 
研究人员对难治DiHS/DRESS患者的皮肤和血液进行了scRNA-seq检测，确定了JAK-STAT信号通路为潜在靶标。研究人员进一步发现，中央记忆CD4+T细胞富含人类疱疹病毒6b的DNA。通过托法替尼的干预使疾病控制和其他免疫抑制剂逐渐减少。托法替尼和抗病毒药在体外抑制了病因引起的T细胞增殖，进一步支持了JAK–STAT途径和疱疹病毒在介导药物不良反应中的作用。因此，scRNA-seq分析指导了难治性DiHS/DRESS患者的成功治疗性干预。 scRNA-seq可能会增进人们对复杂人类疾病病理生理学的理解，并提供个性化医学的替代方法。
 
附：英文原文

Title: Targeted therapy guided by single-cell transcriptomic analysis in drug-induced hypersensitivity syndrome: a case report

Author: Doyoung Kim, Tetsuro Kobayashi, Benjamin Voisin, Jay-Hyun Jo, Keiko Sakamoto, Seon-Pil Jin, Michael Kelly, Helena B. Pasieka, Jessica L. Naff, Jon H. Meyerle, Ijeoma D. Ikpeama, Gary A. Fahle, Fred P. Davis, Sergio D. Rosenzweig, Julie C. Alejo, Stefania Pittaluga, Heidi H. Kong, Alexandra F. Freeman, Keisuke Nagao

Issue&Volume: 2020-01-20

Abstract: Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DiHS/DRESS) is a potentially fatal multiorgan inflammatory disease associated with herpesvirus reactivation and subsequent onset of autoimmune diseases1,2,3,4. Pathophysiology remains elusive and therapeutic options are limited. Cases refractory to corticosteroid therapy pose a clinical challenge1,5 and approximately 30% of patients with DiHS/DRESS develop complications, including infections and inflammatory and autoimmune diseases1,2,5. Progress in single-cell RNA sequencing (scRNA-seq) provides an opportunity to dissect human disease pathophysiology at unprecedented resolutions6, particularly in diseases lacking animal models, such as DiHS/DRESS. We performed scRNA-seq on skin and blood from a patient with refractory DiHS/DRESS, identifying the JAK–STAT signaling pathway as a potential target. We further showed that central memory CD4+ T cells were enriched with DNA from human herpesvirus 6b. Intervention via tofacitinib enabled disease control and tapering of other immunosuppressive agents. Tofacitinib, as well as antiviral agents, suppressed culprit-induced T cell proliferation in vitro, further supporting the roles of the JAK–STAT pathway and herpesviruses in mediating the adverse drug reaction. Thus, scRNA-seq analyses guided successful therapeutic intervention in the patient with refractory DiHS/DRESS. scRNA-seq may improve our understanding of complicated human disease pathophysiology and provide an alternative approach in personalized medicine.

DOI: 10.1038/s41591-019-0733-7

Source: https://www.nature.com/articles/s41591-019-0733-7

Nature Medicine：《自然—医学》，创刊于1995年。隶属于施普林格·自然出版集团，最新IF：87.241
官方网址：https://www.nature.com/nm/
投稿链接：https://mts-nmed.nature.com/cgi-bin/main.plex


本期文章：《自然—医学》：Online/在线发表

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