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

Area of Science:

• Immunology
• Genomics
• Pharmacology

Background:

• Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DiHS/DRESS) is a severe, potentially fatal condition linked to herpesvirus reactivation and autoimmune diseases.
• Current understanding of DiHS/DRESS pathophysiology is limited, and treatment options, especially for corticosteroid-refractory cases, are scarce.
• Approximately 30% of DiHS/DRESS patients experience serious complications like infections and autoimmune disorders.

Observation:

• Single-cell RNA sequencing (scRNA-seq) was employed to investigate the pathophysiology of a patient with refractory DiHS/DRESS.
• scRNA-seq analysis revealed enrichment of human herpesvirus 6B DNA in central memory CD4+ T cells.
• The JAK-STAT signaling pathway was identified as a potential therapeutic target.

Findings:

• Tofacitinib intervention successfully controlled the patient's DiHS/DRESS and allowed for reduction of other immunosuppressants.
• Both tofacitinib and antiviral agents inhibited the proliferation of culprit-induced T cells in vitro.
• These findings implicate the JAK-STAT pathway and herpesviruses in the mechanism of this adverse drug reaction.

Implications:

• scRNA-seq offers a powerful tool for dissecting complex human disease pathophysiology, particularly in conditions lacking animal models.
• Targeting the JAK-STAT pathway and addressing viral reactivation presents a promising therapeutic strategy for refractory DiHS/DRESS.
• This approach may pave the way for personalized medicine interventions in challenging hypersensitivity reactions.