A STAT1-gain-of-function mutation causing Th17 deficiency with chronic mucocutaneous candidiasis, psoriasiform...

Area of Science:

• Immunology
• Genetics
• Infectious Diseases

Background:

• Inborn errors in Interleukin-17 (IL-17) immunity are linked to primary immunodeficiencies causing chronic mucocutaneous candidiasis (CMC).
• Defects in Candida albicans sensing or IL-17 signaling pathways can result in susceptibility to Candida infections.
• CMC can manifest as part of syndromic or isolated immunodeficiency diseases.

Observation:

• A 40-year-old woman presented with recurrent bacterial abscesses, chronic oral candidiasis, and extensive fungal infections.
• Whole exome sequencing revealed a STAT1-gain-of-function mutation in the patient.
• The patient exhibited severely impaired T helper 17 (Th17) cell responses.

Findings:

• A novel STAT1-gain-of-function mutation was identified as the cause of the patient's immunodeficiency.
• The mutation led to a significant impairment in Th17 cell responses.
• The patient's clinical manifestations included bacterial and fungal infections.

Implications:

• This case highlights STAT1-gain-of-function mutations as a cause of CMC and related infections.
• Understanding Th17 cell deficiencies is crucial for diagnosing and managing these primary immunodeficiencies.
• Antifungal and prophylactic antibiotic therapies can effectively manage infections in affected individuals.