DISTRIBUTION OF MHC CLASS-II ALLELES IN PRIMARY SYSTEMIC VASCULITIS

Previous studies have shown a number of different associations between major histocompatibility complex (MHC) alleles and primary systemic v asculitis. Disease heterogeneity and the lack of specificity of certai n MHC typing techniques may have contributed to the lack of consistenc y in those studies. We therefore studied a relatively homogeneous grou p of 94 patients with Wegener's granulomatosis, microscopic polyangiit is, or renal-limited vasculitis using molecular techniques that allow more precise assignment of MHC genotype. DNA was prepared from periphe ral blood and DRB1 genotype determined by Tag restriction fragment len gth polymorphism. DQB1 and DPB1 genotype were assigned by polymerase c hain reaction amplification followed by probing with allele-specific o ligonucleotides. Specificity of associated anti-neutrophil cytoplasm a ntibodies (ANCA) was determined where possible by solid phase immunoas says using purified proteinase 3 (PR3) and myeloperoxidase (MPO). Afte r correction for multiple comparisons there were no significant differ ences in the distribution of DRB1, DQB1 and DPB1 alleles between a loc al control group (N = 90 for DRB1, N = 50 for DQB1 and DPB1) and the p atient group as a whole (N = 94) or two a priori defined subgroups (an ti-PR3 positive, N = 35; anti-MPO positive, N = 22). We have therefore found no significant association between primary systemic vasculitis and any MHC class II allele. This, together with the fact that previou s smaller studies have shown no consistent association, suggests that any such association is very weak, if it exists at all.