Anti-neutrophil cytoplasm antibodies (ANCA) in rheumatoid arthritis: relationship to HLA-DR phenotypes, rheumatoid factor, anti-nuclear antibodies and disease severity.

To investigate a possible relationship between the presence of anti-neutrophil cytoplasm antibodies (ANCA), rheumatoid factors (RF), anti-nuclear antibodies (ANA), disease severity and HLA-DR phenotypes, 46 consecutive ANCA+ and 48 ANCA-, clinically well-documented RA patients were studied for RF, ANA and HLA-DR phenotypes. The 46 ANCA+ patients showed predominantly an atypical perinuclear staining pattern (89%). ANCA positivity was associated with higher RF titres (P < 0.005) and advanced functional Steinbrocker grades III/IV (P < 0.015). ANCA+ patients were also more often positive for ANA than ANCA- patients (P < 0.008). There was no correlation between ANCA positivity and certain HLA-DR phenotypes although the frequency of DR4+ (67% vs 52%) and, in particular, of DR4+ blanks (phenotypically homozygous) was increased in ANCA+ as compared to ANCA- patients (20% vs 8%). DR4-DR1-RA patients were twice as frequent in the ANCA- than in the ANCA+ group (22.9% vs 8.7%). Correspondingly, the DR4+DR1- phenotype was increased among ANCA+ RA patients. Regarding functional Steinbrocker grades, the DR4+ phenotypes were slightly but not significantly increased in grades III and IV whereas ANCA positivity was significantly associated with severe functional Steinbrocker grades III/IV (66% ANCA+ vs 39% ANCA-, P < 0.015). ANCA positivity identified a population of RA patients with a long-standing and severe clinical course of the disease. There was no correlation between ANCA positivity and certain HLA-DR phenotypes.