Abstract
Distortions in frequency distribution of the allotypes of human C3 (C3*S and C3*F) have been linked to disease. Explanations for these associations have invoked the possibility of functional differences between the allotypes. We report the first detailed studies of C3 allotype function and distribution in disease.
Purified C3 of each type was prepared from plasma of homozygous donors. In a standard functional assay with sheep erythrocytes (EA's), the hemolytic efficiency of C3S was 1.3 times that of C3F. Correspondingly, C3S uptake on EA's via the classical C3 convertase (assessed by anti C3c binding) was 1.4 times that of C3F.
Interaction of C3S and C3F with regulators was measured using C3b of each type incubated with purified I and increments of purified H or a source of CR1. No difference in the proteolytic formation of C3bi by each allotype was seen.
Labeled BSA and anti-BSA complexes were solubilized In sera containing an excess of C3S or C3F, and uptake of complexes onto erythrocytes was measured. Uptake at 15 minutes was identical, and no kinetic differences were apparent.
Distribution of C3S and C3F was examined in groups of patients with diseases in which C3 is thought to be involved; SLE.(30), MPGN (33), and IgA nephropathy (31). No significant differences from the distribution of allotypes in 100 healthy controls (C3S =.8; C3F = .2) were evident.
We thus found no association between C3 genetic polymorphism and diseases in which C3 is relevant. More importantly, we identified no important functional differences which could explain such associations, other than trivial differences in affinity for EA's.
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Welch, T., Beischel, L. & West, C. POLYMORPHISM OF HUMAN C3: CLINICAL AND FUNCTIONAL CONSEQUENCES. Pediatr Res 21 (Suppl 4), 320 (1987). https://doi.org/10.1203/00006450-198704010-00917
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DOI: https://doi.org/10.1203/00006450-198704010-00917