[New aspects in ANCA-associated vasculitides].
Wegener's granulomatosis (WG), microscopic polyangiitis, and Churg-Strauss syndrome belong to the group of ANCA-associated vasculitides. Numerous in vitro studies underscored the role of antineutrophil cytoplasmic antibodies (ANCA) in the pathogenesis of vasculitis. More recently, a mouse model provided in vivo evidence of the pathogenic role of ANCA by inducing a vasculitis after the transfer of splenocytes or MPO-ANCA. The target antigens of ANCA, myeloperoxidase (MPO) and proteinase 3 (PR3), are translocated onto the cell surface after priming of neutrophil granulocytes with cytokines. ANCA bind to target antigens and activate neutrophil granulocytes resulting in premature degranulation and endothelial cell damage (ANCA-cytokine sequence theory). Both the F(ab')2 end and the FcgammaR(eceptor) end of the ANCA are involved in activating neutrophil granulocytes. This mode of activation might account for differences to normal neutrophil activation via the FcgammaR. In addition, an expansion of T-cells lacking the co-stimulatory molecule CD28 is seen in WG suggesting an altered cellular immune response. Data from European multicenter studies demonstrated, among other things, that azathioprine can be used for the maintenance of remission after successful induction of remission with cyclophosphamide in ANCA-associated vasculitides.
Lamprecht
Peter
P
Poliklinik für Rheumatologie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, und Rheumaklinik Bad Bramstedt, Lübeck. lamprecht@rheuma-zentrum.de
D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology / Q000502:physiology; D001324:Autoantigens / Q000276:immunology; D001379:Azathioprine / Q000627:therapeutic use; D018106:CD28 Antigens; D015267:Churg-Strauss Syndrome / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology / Q000276:immunology*; D003520:Cyclophosphamide / Q000627:therapeutic use; D004195:Disease Models, Animal; D014890:Granulomatosis with Polyangiitis / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D051379:Mice; D015337:Multicenter Studies as Topic; D053146:Myeloblastin; D018375:Neutrophil Activation; D009195:Peroxidase / Q000276:immunology / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic; D017452:Receptors, IgG / Q000276:immunology; D012074:Remission Induction; D012697:Serine Endopeptidases / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014657:Vasculitis / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology / Q000276:immunology*
D019268:Antibodies, Antineutrophil Cytoplasmic; D001324:Autoantigens; D018106:CD28 Antigens; D007140:Immunoglobulin Fab Fragments; D007166:Immunosuppressive Agents; D017452:Receptors, IgG; D003520:Cyclophosphamide; D009195:Peroxidase; D012697:Serine Endopeptidases; D053146:Myeloblastin; D001379:Azathioprine
Aktuelle Aspekte ANCA-assoziierter Vaskulitiden.