Antibody to a cryptic, solid phase C1Q antigen in membranoproliferative nephritis

Abstract

IgG containing material detected in membranoproliferative nephritis (MPGN) serum with a solid phase (sp) C1q ELISA has been presumed to be immune complexes. However, in serum from 13 MPGN patients containing large amounts of spC1q-binding material, sucrose density ultracentrifugation and sieve chromatography showed spC1q-binding protein to sediment at 78 or cofractionate with IgG. One serum (stored for 12 years) contained, in addition, spC1q-binding material sedimenting at more than 19S. Isolated MPGN IgG was shown to bind to spC1q. SpC1q-binding material could be totally removed from MPGN serum by absorption with BSA-anti-BSA immune precipitates, and by acid elution of the precipitates IgG binding to spC1q could be recovered. F(ab')2, isolated from pepsin digested MPGN IgG, continued to bind spC1q. Binding of MPGN IgG or F(ab')2 to spC1q was not inhibited by 2 M NaCl. Incubation of MPGN serum with 125I C1q followed by sucrose density ultracentrifugation resulted in a peak of radioactivity at 11S, the sedimentation rate of C1q, giving evidence that material binding fluid phase C1q is not present. SpC1q-binding IgG was detected in 54% of 68 MPGN patients. These results indicate that the 7S spC1q-binding IgG represents antibody to a cryptic antigen revealed only when C1q fixes to a solid surface.