Jakinibs for the treatment of immune dysregulation in patients with gain-of-function signal transducer and activator of transcription 1 (STAT1) or STAT3 mutations.

Abstract

Genetic variants in proteins involved in cytokine signaling are now recognized as a cause of overwhelming human immune dysregulation. Autosomal dominant gain-of-function (GOF) mutations in signal transducer and activator of transcription 1 (STAT1) cause a variable clinical phenotype that can include chronic mucocutaneous candidiasis (CMC), susceptibility to dimorphic fungal and invasive viral infections , combined immunodeficiency, autoinflammation, and organ-specific autoimmunity .1,2 STAT3 GOF mutations cause early-onset lymphoproliferation with lymphadenopathy and hepatosplenomegaly and multiorgan autoimmunity , including cytopenias , hepatitis , inflammatory lung disease , enteropathy, hypothyroidism , and diabetes mellitus