title: Individuals with IgA deficiency and common variable immunodeficiency share polymorphisms of major histocompatibility complex class III genes.
abstract: IgA deficiency and common variable immunodeficiency are heritable disorders that can occur within the same family. Both immunodeficiencies are characterized by arrests in B-cell differentiation that vary in the extent of the immunoglobulin isotypes involved. A high frequency of major histocompatibility complex supratypes associated with a null allele of the gene encoding the C4A isotype of complement component C4 has been observed in IgA-deficient individuals. In search of a genetic linkage between the two immunodeficiencies, we examined the major histocompatibility complex (MHC) class III genes encoding complement components C2, C4A, and C4B and steroid 21-hydroxylase in addition to the HLA serotypes in individuals with either common variable immunodeficiency or IgA deficiency. Twelve of 19 patients with common variable immunodeficiency (63%, P less than 0.001) and 9 of 16 patients with IgA deficiency (56%, P less than 0.01) had rare C2 alleles and/or C4A and 21-hydroxylase A deletions, whereas these gene features were seen in only 5 of 34 healthy individuals (15%) in the control group. Nine of 11 patients with C4A deletion had an HLA haplotype consistent with the MHC supratype HLA-A1, Cw7, B8, C4AQ0, C4B1, BfS, DR3 previously found to be associated with IgA deficiency. The data support the hypothesis that common variable immunodeficiency and IgA deficiency are related disorders, susceptibility to which is determined by a gene(s) within or near the MHC class III gene region on chromosome 6.
authors.affiliation: Department of Pediatrics, University of Alabama at Birmingham 35294.
authors.forename: F M
authors.initials: FM
authors.lastname: Schaffer
authors.forename: J
authors.initials: J
authors.lastname: Palermos
authors.forename: Z B
authors.initials: ZB
authors.lastname: Zhu
authors.forename: B O
authors.initials: BO
authors.lastname: Barger
authors.forename: M D
authors.initials: MD
authors.lastname: Cooper
authors.forename: J E
authors.initials: JE
authors.lastname: Volanakis
mesh_terms: D000483:Alleles; D015703:Antigens, CD / Q000032:analysis / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology; D003165:Complement System Proteins / Q000235:genetics; D004406:Dysgammaglobulinemia / Q000150:complications / Q000235:genetics* / Q000276:immunology; D005260:Female; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D006801:Humans; D017098:IgA Deficiency; D007070:Immunoglobulin A / Q000235:genetics; D007153:Immunologic Deficiency Syndromes / Q000150:complications / Q000235:genetics* / Q000276:immunology; D008285:Major Histocompatibility Complex; D008297:Male; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011947:Receptors, Antigen, B-Cell / Q000032:analysis / Q000235:genetics; D012016:Reference Values; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D015703:Antigens, CD; D007070:Immunoglobulin A; D011947:Receptors, Antigen, B-Cell; D003165:Complement System Proteins