title: Discordance between IgA switching at the DNA level and IgA expression at the mRNA level in IgA-deficient patients.
abstract: IgA deficiency is a common immune disorder in Caucasians and is associated with certain MHC conserved extended haplotypes, such as [HLA-B8, SC01, DR3], which presumably carry a susceptibility gene(s). We applied a competitive digestion-circularization PCR method to quantitate the number of switch (S)mu to S alpha rearrangements in peripheral B cells from IgA-deficient subjects homozygous for this haplotype and compared their number with the productive C alpha mRNA level to determine C alpha gene expression in IgA-switched B cells. Two types of defects, low expression of both secreted and membrane forms of productive C alpha mRNA in IgA-switched B cells and impaired IgA switching, were characterized in IgA-deficient subjects homozygous for [HLA-B8, SC01, DR3]. The former defect was also found in another noncarrier subject. It may directly cause low IgA secretion and reflects a blockade in post-IgA switch differentiation of B cells. These results suggest that the heterogeneity of defects in IgA deficiency is not simply ascribable to MHC susceptibility genes.
authors.affiliation: Center for Blood Research, Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.forename: D
authors.initials: D
authors.lastname: Yunis
authors.forename: M
authors.initials: M
authors.lastname: Irigoyen
authors.forename: B
authors.initials: B
authors.lastname: Kitchens
authors.forename: A
authors.initials: A
authors.lastname: Bottaro
authors.forename: F W
authors.initials: FW
authors.lastname: Alt
authors.forename: C A
authors.initials: CA
authors.lastname: Alper
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D001483:Base Sequence; D019013:CD40 Antigens / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D004247:DNA / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression; D015322:Gene Rearrangement, B-Lymphocyte; D006801:Humans; D017098:IgA Deficiency / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D007070:Immunoglobulin A / Q000235:genetics*; D007134:Immunoglobulin Switch Region; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics*; D011995:Recombination, Genetic; D014158:Transcription, Genetic
chemical_list: D019013:CD40 Antigens; D017931:DNA Primers; D007070:Immunoglobulin A; D012333:RNA, Messenger; D016753:Interleukin-10; D015847:Interleukin-4; D004247:DNA