Detection of anti-neutrophil cytoplasmic antibodies in MRL/Mp-lpr/lpr mice and analysis of their target antigens.

Anti-neutrophil cytoplasmic antibodies (ANCA) have been widely studied and recognized to be clinically very important for some human diseases including systemic rheumatic diseases. We analyzed ANCA response and their target antigens in MRL/Mp-lpr/lpr (MRL-lpr) mice, an animal model of systemic rheumatic disease. P-ANCA was detected in 57% of the mice. Antibodies to the known P-ANCA target antigens at the same age were examined. Among these, antibodies to high mobility group (HMG) proteins HMG1 and HMG2 were detected in 57% of the mice, 75% of which were also positive for P-ANCA. These anti-HMG1/HMG2 activities were absorbed by preincubation with a mixture of HMG1 and HMG2. In contrast, antibodies to myeloperoxidase and cathepsin G were detected in 14% and 7%, respectively, but these activities were not inhibited by preincubation with corresponding antigens. In addition, the titers of P-ANCA and anti-HMG1/HMG2 antibodies in MRL-lpr mice were significantly correlated with each other. Thus, HMG1 and HMG2 were considered to be significant target antigens of P-ANCA in MRL-lpr mice.