title: The higher frequency of IgA deficiency among Swedish twins is not explained by HLA haplotypes.
abstract: Serum immunoglobulin A (IgA) concentrations were determined in 12 600 adult Swedish twins, applying a high-throughput reverse-phase protein microarray technique. The prevalence of IgA deficiency (IgAD) was found to be 1:241 in monozygotic (MZ) twins and 1:198 in dizygotic (DZ) twins. Hence, the prevalence in twins is markedly elevated as compared with the normal Swedish adult population (1:600). The twins did not show a difference in the frequency of HLA haplotypes in comparison with almost 40 000 healthy Swedish controls. As expected, the risk-conveying HLA alleles A*01, B*08 and DRB1*01 were overrepresented among the IgAD twins and were also associated with significantly lower mean serum IgA concentrations in the twin cohort. In contrast, significantly higher mean IgA concentrations were found among individuals carrying the protective HLA alleles B*07 and DRB1*15. Exome sequencing data from two MZ twin pairs discordant for the deficiency showed no differences between the siblings. Model fitting analyses derived a heritability of 35% and indicate that genetic influences are modestly important for IgAD. The probandwise concordance rates for IgAD were found to be 31% for MZ and 13% for DZ twins.
authors.affiliation: Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Frankowiack
authors.affiliation: Institute for Molecular Medicine, Finland FIMM, University of Helsinki, Helsinki, Finland.
authors.forename: R-M
authors.initials: RM
authors.lastname: Kovanen
authors.affiliation: Institute for Molecular Medicine, Finland FIMM, University of Helsinki, Helsinki, Finland.
authors.forename: G A
authors.initials: GA
authors.lastname: Repasky
authors.affiliation: Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: C K
authors.initials: CK
authors.lastname: Lim
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Song
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: N L
authors.initials: NL
authors.lastname: Pedersen
authors.affiliation: Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Hammarström
mesh_terms: D000483:Alleles; D004797:Enzyme-Linked Immunosorbent Assay; D059472:Exome; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D017098:IgA Deficiency / Q000097:blood / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D011159:Population Surveillance; D015995:Prevalence; D040081:Protein Array Analysis; D013548:Sweden / Q000453:epidemiology; D014427:Twins; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic
chemical_list: D006680:HLA Antigens; D007070:Immunoglobulin A