Cutaneous Vasculitis and Recurrent Infection Caused by Deficiency in Complement Factor I.

Area of Science:

• Immunology
• Genetics
• Rheumatology

Background:

• Cutaneous leukocytoclastic vasculitis is linked to immune complex deposition and complement system dysregulation.
• While often multifactorial, monogenic autoinflammatory diseases are increasingly recognized as rare causes of vasculitis.

Observation:

• A child with consanguineous parents presented with chronic cutaneous leukocytoclastic vasculitis, recurrent respiratory infections, and hypocomplementaemia.
• A homozygous mutation (p.His380Arg) in the complement factor I (CFI) gene was identified.

Findings:

• The identified CFI mutation led to absent alternative complement pathway activity and reduced classical pathway activity.
• Patients exhibited low serum levels of factor I, C3, and factor H, with normal C4 and C2 levels.
• The same mutation and immunological defects were found in an asymptomatic sibling.

Implications:

• Complement factor I (CFI) deficiency is now recognized as a monogenic cause of vasculitis.
• CFI deficiency should be considered in vasculitis patients with persistently low C3 and normal C4 levels.
• This finding expands the understanding of genetic contributions to vasculitis and immune dysregulation.