Myeloperoxidase autoantibodies distinguish vasculitis mediated by anti-neutrophil 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 myeloperoxidase (MPO) occur in the sera of patients with microscopic angiitis, 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 angiitis. In the present study we show that 22% of female MRL-lpr mice develop MPO autoantibodies. These animals develop a clinical syndrome of vasculitis and glomerulonephritis that is distinct from immune complex disease. Anti-MPO monoclonal antibodies derived from these mice are polyreactive and react with double-stranded DNA. They bind a conformational epitope on human MPO which is also expressed by activated human neutrophils. The results suggest that a subset of MRL-lpr mice develop ANCA-related vasculitis rather than systemic lupus erythematosus and may be used as a model for human microscopic angiitis.