High mobility group (HMG) non-histone chromosomal proteins HMG1 and HMG2 are significant target antigens of perinuclear anti-neutrophil cytoplasmic antibodies in autoimmune hepatitis

Background-High mobility group (HMG) non-histone chromosomal proteins HMG1 and HMG2 have been identified as novel antigens of perinuclear antineutroph il cytoplasmic antibodies (p-ANCAs), and the existence of anti-HMG1 and ant i-HMG2 antibodies in a population of patients with ulcerative colitis has b een reported. Aims-To investigate whether HMG1 and HMG2 are target antigens for p-ANCAs i n autoimmune hepatitis (AIH). Patients-Serum samples from 28 patients with AIH, 44 patients with primary biliary cirrhosis (PBC), 27 patients with chronic hepatitis C, and 23 patie nts with chronic hepatitis B were tested. Methods-ANCAs were detected by routine indirect immunofluorescence (IIF). A nti-HMG1 and anti-HMG2 antibodies were assayed by enzyme linked immunosorbe nt assay. Results-p-ANCAs were detected in 89% (25/28) of patients with AIH, 36% (16/ 44) of patients with PBC, 11% (3/27) of patients with chronic hepatitis C, and 13% (3/23) of patients with chronic hepatitis B. Anti-HMG1 and/or anti- HMG2 antibodies were detected in 89% (25/28) of patients with AIH, 70% (31/ 44) with PBC, 26% (7/27) with chronic hepatitis C, and 9% (2/23) with chron ic hepatitis B. In AIH, anti-HMG1 and/or anti-HMG2 antibodies were detected in 96% (24/25) of p-ANCA positive patients. The p-ANCA staining pattern de tected by IIF using sera from patients with AIH disappeared or decreased in titre after preincubation with a mixture of HMG1/HMG2. The presence and ti tres of those antibodies in AIH correlated significantly with those of p-AN CA, but not with those of antinuclear antibody or anti-smooth muscle antibo dy. Conclusions-HMG1 and HMG2 are significant target antigens of p-ANCA in AIH.