Novel P-ANCA, antibodies to HMG1/HMG2, in inflammatory diseases.
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概要
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Besides proteinase 3 and myeloperoxidase, various target antigens have been identified that anti -neutrophil cytoplasmic antibodies (ANCA) can recognize. We have isolated a new member of perinuclear ANCA (P-ANCA) . Previously, we found that patients with ulcerative colitis (UC) had a novel P-ANCA against neutrophil 28-kD protein. Here, we purified the same antigens from HL-60 lysates by using reversed-phase HPLC. The N-terminus amino acids of these proteins were identical with those of high mobility group (HMG) non-histone chromosomal proteins HMG1 and HMG2. The 28-kD band detected by immunoblotting analysis using patient's serum completery disappeared after preincubation with HMG1/HMG2. A mono-clonal antibody to HMGI/HMG2 stained neutrophils selectivery in a P-ANCA pattern. These results indicate that HMG1/HMG2 can serve as the target antigens of P-ANCA. We then examined serum anti-HMG1/HMG2 antibodies by ELISA. The prevalence of the antibodies were 89% in autoimmune hepatitis, 70% in primary biliary cirrhosis, 48% in rheumatoid arthritis, 45% in systemic lupus erythematosus, and 35% in UC. The occurrence of the antibodies in these diseases seemed to be associated with the disease activity. Thus, anti-HMG1/HMG2 antibodies appear to be useful P-ANCA in some inflammatory diseases, especially in autoimmune liver diseases.
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