Unknown

Dataset Information

0

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.

SUBMITTER: Kim D 

PROVIDER: S-EPMC7105105 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications


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 diseases<sup>1-4</sup>. Pathophysiology remains elusive and therapeutic options are limited. Cases refractory to corticosteroid therapy pose a clinical challenge<sup>1,5</sup> and approximately 30% of patients with DiHS/DRESS develop complications, including infe  ...[more]

Similar Datasets

| S-EPMC6909205 | biostudies-literature
| S-EPMC7841290 | biostudies-literature
| S-EPMC6376473 | biostudies-literature
| PRJEB46193 | ENA
| S-EPMC8189308 | biostudies-literature
| S-EPMC8572576 | biostudies-literature
2020-06-04 | GSE151766 | GEO
| S-EPMC9446077 | biostudies-literature
| S-EPMC6890602 | biostudies-literature
| S-EPMC6716805 | biostudies-literature