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A serum C3-activating factor: its characterization and its presence in glomerular deposits

, : A serum C3-activating factor: its characterization and its presence in glomerular deposits. Journal of Immunology 127(3): 1131-1137

A non-IgG C3 activating factor (C3AF) isolated from the serum and plasma of a patient with membranoproliferative glomerulonephritis with subendothelial and subepithelial deposits (type III) was studied to define its molecular structure, functional characteristics, and presence in renal biopsies. Alternative complement pathway (ACP) activation of C3 was comparable to that of zymosan, but significantly less than that of IgG C3 nephritic factor (C3NeF). Functionally active isolate contained beta 1H globulin (beta 1H) and the C3AF protein, which had a gamma-electrophoretic migration. beta 1H present in the isolate exhibited an altered gamma-beta electrophoretic mobility. The function of this complex is heat labile. Time/temperature studies demonstrated that inactivated preparations of this isolate show a return to the normal beta migration of beta 1H followed by the development of an alpha 2 electrophoretic migration of the previously gamma-migrating material of functionally active isolate. Normal human serums contain an alpha 2 protein that shows complete antigenic identity with the gamma protein of C3AF, but this alpha 2 protein lacks C3 activating function. On polyacrylamide gel electrophoresis, the C3AF isolate contains a high m.w. protein of 500,000 to 590,000 that is composed of 2 major subunits. Carbohydrate is not demonstrable, and the protein is antigenically distinct from plasma fibronectin. Immunofluorescence studies of renal biopsies of patients with types I and III MPGN revealed the presence of C3AF antigen in granular deposits in 10 of 16 cases. The presence of this antigen in glomerular deposits was associated with C3 and beta 1H, but was independent of Ig. These studies suggest that the mechanism of ACP activation by C3AF results from interference with beta 1H function. The presence of this material in renal biopsies from some MPGN patients further suggests a pathogenetic role in mediating glomerular pathology.


PMID: 7021675

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