Reduced C8 beta messenger RNA expression in families with hereditary C8 beta deficiency

Individuals with functional C8 beta deficiency are at increased risk for systemic neisserial infections. Studies by others have shown that the structural gene for this protein appears intact in deficient individuals. We studied affected individuals from 10 unrelated families to determine the basis for their defect. Using chain-specific antisera, C8 beta was undetectable on immunoblots of their sera. The polymerase chain reaction was used to probe cDNA synthesized from RNA isolated from human liver cells, HepG2 cells, peripheral blood monocytes, and fibroblasts to identify a readily available cell source expressing C8 beta message. Cells from each of these sources expressed C8 beta message. The identity of the amplified product was confirmed and this approach was used to probe cDNA synthesized from RNA harvested from monocytes or fibroblasts obtained from two unrelated families with C8 beta deficiency. C8 beta mRNA was readily detectable in C8 beta sufficient and heterozygous family members but required Southern blotting and hybridization to the 32P-labeled C8 beta probe for detection in the homozygous deficient probands. These results suggest that C8 beta-deficient individuals produce less C8 beta-specific mRNA than do normals and that the underlying basis for this deficiency is an abnormality in intracellular events that precede secretion.