IgA Deficiency and the MHC: Assessment of Relative Risk and Microheterogeneity Within the HLA A1 B8, DR3 (8.1) Haplotype
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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.
Materials and 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.
Results and Discussion
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.
KeywordsHLA immunogenetics immunodeficiency IgA deficiency
The study was supported by the Swedish Research Council and grant (U19AI067152) from the US National Institute of Allergy and Infectious Diseases. Javad Mohammadi is supported by an educational grant from the Iranian government. We wish to thank Dr. Leonid Padyukov for careful review of the manuscript. We would also like to thank Drs. Leonid Padyukov and Lars Klareskog at the Rheumatology Unit, Department of Medicine at the Karolinska University hospital Solna, Sweden, for supplying some of the control samples used in this study.
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