Two distinct abnormalities in patients with C8α-γ deficiency. Low level of C8β chain and presence of dysfunctional C8α-γ subunit

The sera from three C8α-γ deficient patients previously reported to have a selective C8α-γ defect were analyzed by SDS-PAGE and Western blot using two polyclonal antisera to C8α-γ and a monoclonal antibody to C8α. All three sera exhibited C8α-γ bands that dissociated into α and γ chains under reducing conditions. Quantitation of the α-γ subunit in these sera by a sensitive ELISA revealed an amount ~1% of that found in normal human serum. A similar assay performed with a specific antiserum to C8β showed unexpectedly low levels of C8β in these sera, which were confirmed by hemolytic titration of C8β. The remarkable differences between C8α-γ and C8β in the C8α-γ deficient sera was that in spite of their comparable immunochemical levels, C8β still exhibited functional activity whereas C8α-γ was totally inactive. That the residual C8α-γ was inactive was also proved by its inability to show lytic bands in an overlay system after SDS-PAGE and subsequent removal of SDS. The implications of these findings for a novel concept of C8 deficiency are discussed.