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

In ANCA-associated small vessel vasculitis few genetic factors have proven to be of importance for disease susceptibility, an exception being deficien cy of alpha(1)-anti-trypsin, the main inhibitor of proteinase 3 (PR3). Aler ted by our finding that myeloperoxidase has affinity for C3, and the findin g of an increased frequency of the C3F allele in systemic vasculitis in a B ritish cohort, we examined polymorphism of C3 and C4 in patients with ANCA( +) small vessel vasculitis. After identification of all patients at our dep artment with a positive ANCA test during the period 1991-95 and a diagnosis of small vessel vasculitis, blood samples were collected after informed co nsent. The 67 included patients were grouped according to ANCA serology and disease phenotype using the Chapel Hill nomenclature. The gene frequency o f C3F was found to be increased (0.32) compared with controls (0.20; P < 0. 05) in the PR3-ANCA(+) subgroup. The frequency of C4A3 was increased in the group as a whole, but no increase of C4 null alleles was seen. The finding s imply a role for the complement system in the pathogenesis of ANCA-associ ated small vessel vasculitis.