title: The [HLA-B18, F1C30, DR3] conserved extended haplotype carries a susceptibility gene for IgD deficiency.
abstract: We showed previously that the conserved extended MHC haplotype [HLA-B8, SCO1, DR3] carries recessive susceptibility genes for IgA and IgG4 deficiency and dominant genes for IgD and IgG3 deficiency. [HLA-B18, F1C30, DR3] has similar 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 (FIC30, DRB1*0301, DRB3*02, DQA1*0501. DQB1*0201) (F1C30, DR3). As shown by others, no subjects were deficient in IgA, IgM, or IgG subclasses. In contrast, 29% of homozygotes and three of seven double heterozygotes with (SC01, DRB1*0301, DRB3*0101, DQA1*0501, DQB1*0201) (presumed homozygotes for IgD deficiency susceptibility genes) were IgD deficient. Thus, 32% of presumed homozygotes were IgD deficient compared with 1.6% of noncarriers. Of haplotype heterozygotes, 25% were IgD deficient. The high frequency of IgD deficiency in both homozygotes and heterozygotes for (F1C30, DR3) suggests a partially penetrant dominant susceptibility gene for IgD deficiency on [HLA-B18, F1C30, DR3].
authors.affiliation: The Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: B
authors.initials: B
authors.lastname: Calvo
authors.forename: L
authors.initials: L
authors.lastname: Castaño
authors.forename: D
authors.initials: D
authors.lastname: Marcus-Bagley
authors.forename: D A
authors.initials: DA
authors.lastname: Fici
authors.forename: Z
authors.initials: Z
authors.lastname: Awdeh
authors.forename: C A
authors.initials: CA
authors.lastname: Alper
mesh_terms: D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology; D004406:Dysgammaglobulinemia / Q000235:genetics* / Q000276:immunology*; D005260:Female; D006680:HLA Antigens / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics*; D059911:HLA-B18 Antigen; D015803:HLA-DR3 Antigen / Q000235:genetics*; D006239:Haplotypes; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007072:Immunoglobulin D / Q000097:blood / Q000172:deficiency*; D008297:Male; D010375:Pedigree; D013030:Spain
chemical_list: D006680:HLA Antigens; D015235:HLA-B Antigens; D059911:HLA-B18 Antigen; D015803:HLA-DR3 Antigen; C062341:HLA-F antigens; D015395:Histocompatibility Antigens Class I; D007072:Immunoglobulin D