Experimental Models of Vasculitis and Glomerulonephritis Induced by Antineutrophil Cytoplasmic Autoantibodies

摘要: Antineutrophil cytoplasmic autoantibodies (ANCA) are closely associated with systemic small vessel vasculitis characterized by segmental wall necrotizing inflammation and a paucity of immunoglobulin deposition. Clinically, in vitro experimental animal model observations indicate direct pathogenic role for ANCA. This review focuses on the results experiments utilizing mouse ANCA disease induced transfer anti-MPO IgG or lymphocytes into recipient mice, which causes glomerulonephritis that mimics human disease. Evidence following conclusion about this model, implication disease, will be summarized as follows: (1) is sufficient even absence functional T cells to cause not acute injury; (2) neutrophils required; (3) antigens bone marrow-derived targets; (4) increased circulating pro-inflammatory cytokines microbial products exacerbate concurrent viral infection exacerbates modulates phenotype disease; (5) Fcγ receptor engagement required induction, repertoire especially pulmonary (6) activation alternative pathway complement required, activated factors released stimulated C5a receptors primary event complement-mediated amplification; (7) genetic background has marked influence severity outcome modified gene expression basis genetically determined differences susceptibility. Investigations using have provided important insights cellular, molecular involved pathogenesis likely lead identification improved markers activity response therapy, well more effective less toxic therapies.