MYELOPEROXIDASE AUTOANTIBODIES DISTINGUISH VASCULITIS MEDIATED BY ANTINEUTROPHIL CYTOPLASM ANTIBODIES FROM IMMUNE-COMPLEX DISEASE IN MRL MP-LPR/LPR MICE - A SPONTANEOUS MODEL FOR HUMAN MICROSCOPIC ANGIITIS/

Anti-neutrophil cytoplasm antibodies (ANCA) with specificity for myelo peroxidase (MPO) occur in the sera of patients with microscopic angiit is, an autoimmune disease characterized by necrotizing vasculitis and crescentic glomerulonephritis. These autoantibodies have been shown to stimulate neutrophil degranulation and are believed to participate in pathogenesis. A neutrophilic vasculitis has been reported in MRL-lpr mice which has histological appearances similar to microscopic angiiti s. In the present study we show that 22 % of female MRL-lpr mice devel op MPO autoantibodies. These animals develop a clinical syndrome of va sculitis and glomerulonephritis that is distinct from immune complex d isease. Anti-MPO monoclonal antibodies derived from these mice are pol yreactive and react with double-stranded DNA. They bind a conformation al epitope on human MPO which is also expressed by activated human neu trophils. The results suggest that a subset of MRL-lpr mice develop AN CA-related vasculitis rather than systemic lupus erythematosus and may be used as a model for human microscopic angiitis.