NON-IMMUNOGLOBULIN-C3 ACTIVATING FACTOR IN MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS

Material isolated by cryoprecipitation from the serum of a patient with membranoproliferative glomerulonephritis exhibited alternative complement pathway C3-splitting activity associated with a nonimmunoglobulin γ-migrating protein. The cryoprecipitate required factor B and magnesium ions, but not C1, C2, or calcium ions for activity. Antiserum produced against the cryoprecipitate recognised a previously unidentified γ-migrating material, as well as β1H globulin (C3b inactivator-accelerator), and kappa light chains. Immunoglobulin (Ig) G was present in trace quantities. Immunoadsorption with antisera to human γ heavy chains or kappa light chains did not alter C3 activation by the resolubilized material. The γ-migrating material, which appears to be an altered form of a normal α2 protein, retains its C3 splitting property when separated from β1H and IgG by sucrose density ultracentrifugation. Antisera monospecific to β1H and to the γ-migrating material each produced intense glomerular immunofluorescence in the patient's renal biopsy in a pattern similar to that of anti-C3. No glomerular staining occurred with antihuman IgG, M, A, E, Clq, C4 or C2. It is proposed that interaction between this protein and β1H in the circulation and in the glomerulus could block β1H-dependent decay-dissociation of C3 convertases, resulting in unregulated alternative complement pathway C3 activation and complement-mediated glomerular damage.