Detection of anti-neutrophil cytoplasmic antibodies in MRL/Mp-lpr/lpr miceand 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 includin g systemic rheumatic diseases. We analyzed ANCA response and their target a ntigens in MRL/Mp-lpr/lpr (MRL-lpr) mice, an animal model of systemic rheum atic disease. P-ANCA was detected in 57% of the mice. Antibodies to the kno wn P-ANCA target antigens at the same age were examined. Among these, antib odies 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-HMG 1/HMG2 activities were absorbed by preincubation with a mixture of HMG1 and HMG2. In contrast, antibodies to myeloperoxidase and cathepsin G were dete cted in 14% and 7%, respectively, but these activities were not inhibited b y preincubation with corresponding antigens. In addition, the titers of P-A NCA and anti-HMG1/HMG2 antibodies in MRL-lpr mice were significantly correl ated with each other. Thus, HMG1 and HMG2 were considered to be significant target antigens of P-ANCA in MRL-lpr mice.