Case report: Myocarditis in congenital STAT1 gain-of function

Front Immunol. 2023 Mar 20:14:1095595. doi: 10.3389/fimmu.2023.1095595. eCollection 2023.

Abstract

Autosomal dominant Signal transducer and activator of transcription 1 (STAT1) gain-of-function (GOF) mutations result in an inborn error of immunity characterized by chronic mucocutaneous candidiasis, recurrent viral and bacterial infections, and diverse autoimmune manifestations. Current treatment consists of chronic antifungal therapy, antibiotics for concomitant infections, and immunosuppressive therapy in case of autoimmune diseases. More recently, treatment with Janus kinases 1 and 2 (JAK1/2) inhibitors have shown promising yet variable results. We describe a STAT1 GOF patient with an incidental finding of elevated cardiac troponins, leading to a diagnosis of a longstanding, slowly progressive idiopathic myocarditis, attributed to STAT1 GOF. Treatment with a JAK-inhibitor (baricitinib) mitigated cardiac inflammation on MRI but was unable to alter fibrosis, possibly due to the diagnostic and therapeutic delay, which finally led to fatal arrhythmia. Our case illustrates that myocarditis could be part of the heterogeneous disease spectrum of STAT1 GOF. Given the insidious presentation in our case, a low threshold for cardiac evaluation in STAT1 GOF patients seems warranted.

Keywords: STAT1 GOF; chronic mucocutaneous candidiasis; infectious susceptibility; myocarditis; primary immunodeficiencies.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoimmune Diseases*
  • Candidiasis, Chronic Mucocutaneous* / genetics
  • Gain of Function Mutation
  • Humans
  • Myocarditis*
  • STAT1 Transcription Factor / metabolism

Substances

  • STAT1 protein, human
  • STAT1 Transcription Factor

Grants and funding

FS (11B5520N), SG (1S23017N), CH (1S07023N) are fellows of the Fonds Wetenschappelijk Onderzoek - Vlaanderen National Fund for Scientific Research (FWO). RS and IM are FWO senior clinical investigator fellow (1805518N and 1805523N, 1805821N). XB, AL, SH-B, IM, and RS are supported by the VIB Grand Challenge program (Translational science initiative on PID, GC01-C01). RS is supported by the FWO project financing (G054022N). IM and RS are members of the European Reference Network for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (Project ID No 739543).