Infections in Inborn Errors of STATs

Abstract

The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is highly conserved and essential for numerous biological functions triggered by extracellular signals, including cell proliferation, metabolism, immune response, and inflammation. Defects in STATs, either loss-of-function or gain-of-function defects, lead to a broad spectrum of clinical phenotypes in humans, including a wide range of infectious complications. The susceptibility to pathogens can stem from defects in immune cells within the hematopoietic compartment, impaired barrier functions of non-hematopoietic compartment, or a combination of both, depending on the specific STAT defect as well as the pathogen exposure history. Effective management involves antimicrobial prophylaxis tailored to the patient's infection risk and improving disease control with targeted therapies and/or hematopoietic cell transplantation.

Keywords: STAT; antimicrobials; hematopoietic cell transplantation; pathogen.

Figure 1

Spectrum of infection susceptibility based on anatomical sites in patients with inborn errors of STATs. STAT2 “GOF” is not included due to the limited number of reported cases, and infection susceptibility is not a primary feature in these patients. The “gray” box indicates a lack of data from published case series, which likely suggests no significantly increased risk beyond that of the general population. GI, gastrointestinal; CNS, central nerve system.

Figure 2

Clinical images of STAT1 GOF and STAT3 HIES: (A) brain MRI showing white matter changes due to John Cunningham virus-related progressive multifocal leukoencephalopathy (PML) in a 30-year-old male with STAT1 GOF; (B) esophageal candidiasis seen in an endoscopy of a 34-year-old male with STAT1 GOF; (C) S. aureus lobar pneumonia in a 40-year-old woman with STAT3 HIES; and (D) pneumatocele complicated by an aspergilloma in a 24-year-old male with STAT3 HIES.