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

Authors
 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 
Citation
 NATURE MEDICINE, Vol.26(2) : 236-243, 2020 
Journal Title
NATURE MEDICINE
ISSN
 1078-8956 
Issue Date
2020
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 diseases1-4. 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.
Full Text
https://www.nature.com/articles/s41591-019-0733-7
DOI
10.1038/s41591-019-0733-7
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Do Young(김도영) ORCID logo https://orcid.org/0000-0002-0194-9854
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/175511
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