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Publication : 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.

First Author  Harper JM Year  1998
Journal  Eur J Immunol Volume  28
Issue  7 Pages  2217-26
PubMed ID  9692891 Mgi Jnum  J:49317
Mgi Id  MGI:1277322 Doi  10.1002/(SICI)1521-4141(199807)28:07<2217::AID-IMMU2217>3.0.CO;2-P
Citation  Harper JM, et al. (1998) 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. Eur J Immunol 28(7):2217-26
abstractText  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.
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