Complement activation by circulating serum factors in human glomerulonephritis.
Factors with the ability to induce a minimum of 20% C3 conversion in normal human serum (NHS) were demonstrated in the sera of nine glomerulonephritis (GN) patients. The nature of these factors was heterogeneous allowing their division into at least three different groups. First, in three cases (membranoproliferative or acute GN) they exhibited the characteristics of C3 nephritic factor, an IgG autoantibody stabilizing the alternative pathway (AP) C3 convertase, C3bBb. Secondly, the serum of one patient (SLE like syndrome, mixed cryoglobulinaemia) with an activator of both pathways and profound hypocomplementaemia showed a temperature-dependent precipitation against autologous and homologous polyclonal IgG. Immunochemical analysis suggested this activity to be due to a monoclonal IgM kappa rheumatoid factor. By gel filtration the C3 converting activity was found in the high molecular weight fractions containing the cryoprecipitable IgM-IgG complexes. Finally, in five cases the exact nature of C-activating factors remained unknown. In four of these the factors were heat labile (30 min at 54 degrees C) C activators in association with post-streptococcal glomerulonephritis. The results suggest that the various C activating factors, possibly distinct from 'classical' immune complexes, are indicators of different types of pathogenetic mechanisms in certain forms of GN.
D000328:Adult; D002648:Child; D002850:Chromatography, Gel; D003166:Complement Activating Enzymes / Q000378:metabolism*; D003167:Complement Activation; D003176:Complement C3 / Q000378:metabolism*; D005260:Female; D005921:Glomerulonephritis / Q000276:immunology*; D006462:Hemolytic Plaque Technique; D006801:Humans; D005779:Immunodiffusion; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D008297:Male; D013997:Time Factors
D003176:Complement C3; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D003166:Complement Activating Enzymes