Prevalence and characterization of novel pANCA, antibodies to the high mobility group non-histone chromosomal proteins HMG1 and HMG2, in systemic rheumatic diseases

OBJECTIVE: To determine the immunodiagnostic value of antibodies to the high mobility group non-histone chromosomal proteins HMG1 and HMG2, which have been identified as novel target antigens of perinuclear antineutrophil cytoplasmic antibodies (pANCA), in sera from patients with systemic rheumatic diseases. METHODS: Anti-HMG1 or HMG2 antibody was assayed by ELISA and Western blotting in sera from patients with systemic rheumatic diseases. These antibodies were analyzed for the relationship with pANCA detected by indirect immunofluorescence in these diseases, and with clinical features in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). RESULTS: Anti-HMG1 or HMG2 antibody was frequently detected in sera from patients with RA (48%), SLE (45%), Sj?gren's syndrome (SS) (44%), and systemic sclerosis (SSc) (41%). In these diseases, anti-HMG1 antibody was detected more frequently than anti-HMG2 antibody. In sera from patients with RA, the positivity for anti-HMG1 and HMG2 antibodies was significantly correlated with the positivity for pANCA (p < 0.0001). Anti-HMG1/HMG2 antibodies were associated with some disease activity variables, e.g., erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, joint score and hand grip strength in RA, and CH50, C3, C4, and IgG in SLE. CONCLUSION: Anti-HMG1/HMG2 antibodies are detected commonly in systemic rheumatic diseases, particularly in RA, SLE, SS, and SSc. HMGI and HMG2 seem to be the significant target antigens of pANCA in RA. These antibodies are significantly associated with disease activity indices in RA and SLE.