The [HLA-B18, F1C30, DR3] conserved extended haplotype carries a susceptibility gene for IgD deficiency

We showed previously that the conserved extended MHC haplotype [HLA-B8 SC01 , DR3] carries recessive susceptibility genes for IgA and IgG4 deficiency a nd dominant genes for IgD and IgG3 deficiency. [HLA-B18: F1C30, DR3] has si milar class II and III regions to [HLA-B8, SC01, DR3] and is common in the Basques. We therefore studied serum immunoglobulin concentrations in Basque homozygotes, heterozygotes, and noncarriers of (F1C30, DRB1*0301, DRB3*02, DQA1*0501, DQB1*0201) (FIC30, DR3). As shown by others, no subjects were d eficient in IgA, IgM, or Ige subclasses. In contrast, 29% of homozygotes an d three of seven double heterozygotes with (SC01, DRB1*0301, DRB3*0101, DQA 1*0501, DQB1*0201) (presumed homozygotes for IgD deficiency susceptibility genes) were IgD deficient. Thus, 32% of presumed homozygotes were IgD defic ient compared with 1.6% of noncarriers. Of haplotype heterozygotes, 25% wer e IgD deficient. The high frequency of IgD deficiency in both homozygotes a nd heterozygotes for (F1C30, DR3) suggests a partially penetrant dominant s usceptibility gene far IgD deficiency on [HLA-B18, FlC30, DR3].