Specific immunoabsorption.
Rapidly progressive glomerulonephritis occurs in patients developing autoantibodies to the glomerular basement membrane (GBM) and in multisystem vasculitic syndromes such as Wegener's granulomatosis (WG) and microscopic polyarteritis (MPA). In anti-GBM disease the pathogenicity of the autoantibodies has been established by transfer experiments; new solid-phase radioimmunoassays (RIAs) for circulating autoantibodies allow early diagnosis and effective monitoring of treatment. Sequential measurements of antibody levels showed that their generation is self-limiting (even without treatment) and that their production can be arrested more quickly with immunosuppressive therapy (cyclophosphamide and high dose steroids) together with intensive plasma exchange. In systemic vasculitis, no pathogenic agent has been identified and the diseases are rarely self-remitting. In WG, antibodies to cytoplasmic components of normal human neutrophils (and monocytes) were reported to be detectable by indirect immunofluorescence, with titres correlating with disease activity. We confirmed this and showed that antigen can be extracted from normal human neutrophils and used as ligand in a solid-phase RIA. Sera from patients with other forms of systemic vasculitis, such as MPA, as well as WG, are positive in this assay. The antigens have been further characterized by HPLC fractionation on a Toyosoda TSK gel filtration column. In WG, antibodies were directed towards cytoplasmic fractions of 100, 6 and 2 kDa; in MPA, antibody reacted only with the 100 kDa fraction. These findings suggest a humoral pathogenesis in these disorders and indicate that this approach may be helpful in the classification, diagnosis and monitoring of therapy in the systemic vasculitides. Further characterization of the autoantigen and its potential use in specific immunoabsorption are discussed.
Lockwood
C M
CM
Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Savage
C O
CO
Pusey
C D
CD
D000469:Alkaline Phosphatase / Q000276:immunology; D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology / Q000628:therapy*; D000936:Antigen-Antibody Complex / Q000627:therapeutic use*; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology / Q000302:isolation & purification; D001485:Basement Membrane / Q000276:immunology; D006801:Humans; D007164:Immunosorbents / Q000627:therapeutic use*; D007678:Kidney Glomerulus / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D014657:Vasculitis / Q000209:etiology / Q000276:immunology
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D001324:Autoantigens; D007164:Immunosorbents; D000469:Alkaline Phosphatase