C3 and C4 allotypes in anti-neutrophil cytoplasmic autoantibody (ANCA)-positive vasculitis

Area of Science:

• Immunogenetics
• Rheumatology
• Complement System Biology

Background:

• Few genetic factors influence ANCA-associated small vessel vasculitis susceptibility.
• Alpha1-anti-trypsin deficiency is a known exception.
• Previous findings suggested myeloperoxidase affinity for C3 and increased C3F allele frequency in systemic vasculitis.

Purpose of the Study:

• To investigate the role of complement system component C3 and C4 gene polymorphisms in ANCA-associated small vessel vasculitis.
• To examine C3 and C4 polymorphism in patients with ANCA-positive small vessel vasculitis.

Main Methods:

• Patients with ANCA-positive small vessel vasculitis (n=67) were identified between 1991-1995.
• Blood samples were collected after informed consent.
• Patients were grouped by ANCA serology and disease phenotype (Chapel Hill nomenclature); C3 and C4 gene frequencies were analyzed.

Main Results:

• The C3F allele frequency was significantly increased (0.32) in the proteinase 3-ANCA positive (PR3-ANCA+) subgroup compared to controls (0.20; P < 0.05).
• An increased frequency of C4A3 was observed in the overall patient group.
• No increase in C4 null alleles was detected.

Conclusions:

• The findings suggest a significant role for the complement system, particularly C3, in the pathogenesis of ANCA-associated small vessel vasculitis.
• The increased C3F allele frequency in PR3-ANCA+ patients warrants further investigation into complement pathways.
• Complement component C4 also appears to be involved, though further study is needed.