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The effect of null C4 alleles on complement function.

T R Welch, L Beischel, A Berry

    Clinical Immunology and Immunopathology
    |March 1, 1985
    PubMed
    Summary
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    The complement component C4 (C4) has common unexpressed alleles (nulls). Studies suggest null C4 genes do not significantly impair complement function, but may link to diseases via HLA haplotypes.

    Area of Science:

    • Immunogenetics
    • Complement System Biology

    Background:

    • Complement component 4 (C4) is encoded by polymorphic C4A and C4B genes.
    • Unexpressed alleles, termed 'nulls', are common and have been linked to various diseases.

    Purpose of the Study:

    • To investigate the functional impact of C4 null alleles.
    • To explore potential mechanisms linking C4 null genes to disease susceptibility.

    Main Methods:

    • Assessed C4 allotypes and hemolytic efficiencies in 75 healthy individuals.
    • Quantified C4 antigenic levels and in vitro C3 convertase formation kinetics.

    Main Results:

    • Mean C4 levels correlated with gene product number, but with significant individual variation.
    • Homozygous C4A null individuals showed higher hemolytic efficiency; C4B null individuals showed lower efficiency compared to those with four gene products.

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  • No differences in C3 convertase formation kinetics were observed between C4A or C4B homozygous null individuals.

    • Conclusions:

    • Null C4 genes do not appear to compromise overall complement function sufficiently to explain disease associations.
    • Disease associations may arise from genetic linkage between C4 null alleles and susceptibility genes within extended HLA haplotypes.