Human C81 (alpha-gamma) polymorphism: detection in the alpha-gamma subunit on SDS-PAGE, formal genetics and linkage relationship.

The molecular basis of human C81 (alpha-gamma) polymorphism could be elucidated by immunoprecipitation of human C81 allotypes and separation of the alpha-gamma and beta subunits on sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) under nonreducing conditions. If the C8 molecules were completely reduced, C81 polymorphism was no longer detectable on SDS-PAGE. It is concluded that C81 variation depends on charge rather than molecular weight differences. Four C81 allotypes, the common A and B and two rare allotypes provisionally named A2 and B1, could be distinguished. The rare allotype A1 as detected by isoelectric focusing with subsequent C8 (alpha-gamma)-dependent functional overlay could no longer be visualized on SDS-PAGE. This allotype may therefore be elicited only in the intact C8 molecule. The beta-chain polymorphism named C82, probably also reflecting charge variation of the C8 molecule, could not be detected yet on SDS-PAGE. The distributions of C81 phenotypes and their respective allele frequencies were in good agreement with previously reported data. In the study of 30 families with 100 offspring, no deviation from the rule of at least four codominant alleles at one genetic locus was found. Linkage between C81 gene(s) and PGM1a encoded on chromosome 1 could be confirmed. The following estimates were obtained: (formula; see text) with S theta being the standard error of the maximum likelihood estimate theta. The new technique for allotyping human C81 at the subunit may provide a new tool for the differentiation of qualitative and quantitative variation of the eighth component of human complement.

Partial C4 deficiency in subacute sclerosing panencephalitis.

In an immunogenetic study, 23 subacute sclerosing panencephalitis (SSPE) patients and their families were studied for the HLA region markers HLA-A, B, C, DR, BF, C2, C4A, C4B, GLO I, and PGM3. In addition, C3, C4, and factor B serum levels were determined. A highly significant association of C4A QO with SSPE was found. Furthermore, two rare haplotypes, C4A QOB QO, two C4ACh+ allotypes, and four Ch partial inhibitors were detected, which possibly impair the function of the C4 molecules. HLA-DR5 was increased. In addition, a number of rare HLA-A, C, B, DR haplotypes were observed. It is postulated that rare C4 molecular deficiency might be a predisposing factor in the pathogenesis of SSPE.