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

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.

journal_name

Nat Med

journal_title

Nature medicine

authors

Kim D,Kobayashi T,Voisin B,Jo JH,Sakamoto K,Jin SP,Kelly M,Pasieka HB,Naff JL,Meyerle JH,Ikpeama ID,Fahle GA,Davis FP,Rosenzweig SD,Alejo JC,Pittaluga S,Kong HH,Freeman AF,Nagao K

doi

10.1038/s41591-019-0733-7

subject

Has Abstract

pub_date

2020-02-01 00:00:00

pages

236-243

issue

2

eissn

1078-8956

issn

1546-170X

pii

10.1038/s41591-019-0733-7

journal_volume

26

pub_type

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