Pathogenesis of PR3-ANCA associated vasculitis.
Wegener's Granulomatosis (WG) is closely associated with antineutrophil cytoplasmic autoantibodies (ANCA), particularly those directed to proteinase 3 (PR3). ANCA directed to myeloperoxidase (MPO) are associated with microscopic polyangiitis (MPA) and the Churg Strauss syndrome. PR3-ANCA associated vasculitis differs from MPO-ANCA associated vasculitis particularly in the occurrence of granulomatous inflammation and more widespread disease in the former condition. Studies in experimental animals strongly suggest a pathogenic role for MPO-ANCA, but this is less clear for PR3-ANCA. Here, we review pathogenic pathways in PR3-ANCA associated vasculitis focussing on unique patterns of PR3 expression on the neutrophil membrane in WG, as surface expression of PR3 is a prerequisite for stimulation by PR3-ANCA; (PR3-specific) cellular immunity in WG; and the role of Staphylococcus aureus carriage in this disease. These factors, together, may explain, at least in part, differences in clinical expression between MPO-ANCA and PR3-ANCA associated vasculitis.
Kallenberg
C G M
CG
Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. c.g.m.kallenberg@int.umcg.nl
D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology* / Q000378:metabolism; D015267:Churg-Strauss Syndrome / Q000276:immunology; D014890:Granulomatosis with Polyangiitis / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D053146:Myeloblastin / Q000276:immunology* / Q000378:metabolism; D018375:Neutrophil Activation; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D009195:Peroxidase / Q000276:immunology* / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology; D014657:Vasculitis / Q000276:immunology* / Q000503:physiopathology
D019268:Antibodies, Antineutrophil Cytoplasmic; D009195:Peroxidase; D053146:Myeloblastin