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

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 1 – 4 . Pathophysiology remains elusive and therapeuti...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Nature medicine Jg. 26; H. 2; S. 236 - 243
Hauptverfasser:	Kim, Doyoung, Kobayashi, Tetsuro, Voisin, Benjamin, Jo, Jay-Hyun, Sakamoto, Keiko, Jin, Seon-Pil, Kelly, Michael, Pasieka, Helena B., Naff, Jessica L., Meyerle, Jon H., Ikpeama, Ijeoma D., Fahle, Gary A., Davis, Fred P., Rosenzweig, Sergio D., Alejo, Julie C., Pittaluga, Stefania, Kong, Heidi H., Freeman, Alexandra F., Nagao, Keisuke
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	New York Nature Publishing Group US 01.02.2020 Nature Publishing Group
Schlagworte:	631/1647/514/1949 631/250 631/250/249/2510 692/308 692/420 692/420/256 692/699 692/699/249/2510 Activation Adrenal Cortex Hormones - therapeutic use Adult Animal diseases Animal models Antiviral agents Antiviral Agents - therapeutic use Antiviral drugs Autoimmune Diseases - complications Biomedical and Life Sciences Biomedicine Cancer Research Case reports CD4 antigen CD4-Positive T-Lymphocytes - cytology Cell Proliferation Cell Separation Complications and side effects Corticosteroids Deoxyribonucleic acid Disease Disease control DNA Drug Hypersensitivity Syndrome - therapy Eosinophilia Flow Cytometry Gene expression Gene sequencing Genetic aspects Genetic transcription Growth Health aspects Herpesvirus 6, Human - immunology Humans Hypersensitivity Immunological memory Immunomodulators Immunosuppressive agents Immunosuppressive Agents - therapeutic use Infectious Diseases Inflammatory diseases Letter Leukocytes, Mononuclear - cytology Lymphocytes Lymphocytes - cytology Lymphocytes T Male Memory cells Metabolic Diseases Molecular Medicine Neurosciences Pathophysiology Patients Piperidines - therapeutic use Precision medicine Pyrimidines - therapeutic use Pyrroles - therapeutic use Ribonucleic acid RNA RNA-Seq Signal Transduction Signs and symptoms Single-Cell Analysis T-Lymphocytes, Regulatory - cytology Tapering Therapy Tofacitinib Transcriptome VDJ Recombinases - metabolism United States
ISSN:	1078-8956, 1546-170X, 1546-170X
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	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 1 – 4 . Pathophysiology remains elusive and therapeutic options are limited. Cases refractory to corticosteroid therapy pose a clinical challenge 1 , 5 and approximately 30% of patients with DiHS/DRESS develop complications, including infections and inflammatory and autoimmune diseases 1 , 2 , 5 . Progress in single-cell RNA sequencing (scRNA-seq) provides an opportunity to dissect human disease pathophysiology at unprecedented resolutions 6 , 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. Single-cell RNA sequencing facilitates successful therapeutic treatment of a patient with a rare and severe drug-induced inflammatory skin reaction.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Case Study-2 ObjectType-Feature-4 content type line 23 ObjectType-Report-1 ObjectType-Article-3
ISSN:	1078-8956 1546-170X 1546-170X
DOI:	10.1038/s41591-019-0733-7