title: IgA deficiency and the MHC: assessment of relative risk and microheterogeneity within the HLA A1 B8, DR3 (8.1) haplotype.
abstract: BACKGROUND
  Selective IgA deficiency (IgAD; serum IgA concentration of <0.07 g/l) is the most common primary immunodeficiency in Caucasians with an estimated prevalence of 1/600. The frequency of the extended major histocompatibility complex haplotype HLA A1, B8, DR3, DQ2 (the "8.1" haplotype) is increased among patients with IgAD.
  
  
  METHODS
  We carried out a direct measurement of the relative risk of homozygosity of the 8.1 haplotype for IgA deficiency in a population-based sample of 117 B8, DR3 homozygous individuals.
  
  
  CONCLUSIONS
  IgA deficiency was found to be present in 2 of 117 (1.7%) of these subjects, a figure that is concordant with estimates of relative risk from large case-control studies in the Swedish population. These data are consistent with a multiplicative model for the 8.1 haplotype contribution to IgA deficiency and contrasts with prior studies, suggesting a much higher risk for 8.1 homozygosity. Using a dense single nucleotide polymorphism marker analysis of the MHC region in HLA B8, DR3, DQ2 homozygous individuals, we did not observe consistent differences between cases (n = 26) and controls (n = 24). Overall, our results do not support the hypothesis that IgA deficiency is associated with a distinct subgroup of 8.1 related haplotypes, but rather indicate that risk is conferred by the common 8.1 haplotype acting in multiplicative manner.
authors.affiliation: Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Javad
authors.initials: J
authors.lastname: Mohammadi
authors.forename: Ryan
authors.initials: R
authors.lastname: Ramanujam
authors.forename: Sara
authors.initials: S
authors.lastname: Jarefors
authors.forename: Nima
authors.initials: N
authors.lastname: Rezaei
authors.forename: Asghar
authors.initials: A
authors.lastname: Aghamohammadi
authors.forename: Peter K
authors.initials: PK
authors.lastname: Gregersen
authors.forename: Lennart
authors.initials: L
authors.lastname: Hammarström
mesh_terms: D003198:Computer Simulation; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D018740:Genetic Heterogeneity; D005828:Genetics, Population; D015788:HLA-A1 Antigen / Q000235:genetics; D015795:HLA-B8 Antigen / Q000235:genetics; D015803:HLA-DR3 Antigen / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D017098:IgA Deficiency / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D007070:Immunoglobulin A / Q000378:metabolism*; D015995:Prevalence; D012306:Risk; D018401:Sample Size; D013548:Sweden; D044465:White People
chemical_list: D015788:HLA-A1 Antigen; D015795:HLA-B8 Antigen; D015803:HLA-DR3 Antigen; D007070:Immunoglobulin A