Association of immunoglobulin A deficiency and elevated thyrotropin-receptor autoantibodies in two Nordic countries

Hum Immunol. 2011 Feb;72(2):166-72. doi: 10.1016/j.humimm.2010.10.014. Epub 2010 Oct 25.


Immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency, with suggested association with various types of autoimmunity, including Graves' disease. This study investigated the association of IgAD with elevated thyrotropin-receptor autoantibodies (TRAb). IgA was measured in TRAb-seropositive individuals from both Iceland (N = 299] and Sweden (N = 841]. In addition, TRAb levels were evaluated in 43 Icelandic and 50 Swedish IgAD individuals using Medizym TRA immunoassay, and positive samples were re-evaluated using BRAHMS TRAK human RIA. The IgAD individuals were HLA-genotyped to determine the HLA-B, DR, and DQ alleles. None of the 299 Icelandic TRAb-seropositive individuals had IgAD, whereas, a high prevalence of IgAD (14/841 (1:60)) was observed in the Swedish cohort (p = 0.027). The prevalence of TRAb-seropositivity in IgAD individuals was, however, increased in both cohorts. The HLA-DQ6 allele was associated with TRAb-seronegativity within the Icelandic IgAD cohort (p = 0.037). The prevalence of IgAD in TRAb-seropositive individuals in Sweden is 10 times higher than expected in the general population. Furthermore, TRAb seropositivity is common among IgAD individuals, both in Iceland and Sweden, suggesting a predisposition toward Graves' disease. These findings underline the significant association of IgAD with autoimmunity and its possible association with certain HLA-DQ alleles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Autoantibodies / genetics
  • Autoantibodies / immunology*
  • Autoimmunity / genetics
  • Female
  • Gene Frequency
  • Genetic Association Studies*
  • Genetic Predisposition to Disease
  • Graves Disease / epidemiology
  • Graves Disease / genetics
  • Graves Disease / immunology*
  • HLA-B Antigens / genetics
  • HLA-B Antigens / immunology
  • HLA-DQ Antigens / genetics
  • HLA-DQ Antigens / immunology
  • HLA-DR Antigens / genetics
  • HLA-DR Antigens / immunology
  • Humans
  • Iceland
  • IgA Deficiency / genetics
  • IgA Deficiency / immunology*
  • Immunoglobulin A / blood
  • Male
  • Middle Aged
  • Prevalence
  • Radioimmunoassay
  • Receptors, Thyrotropin / genetics
  • Receptors, Thyrotropin / immunology*
  • Sweden


  • Autoantibodies
  • HLA-B Antigens
  • HLA-DQ Antigens
  • HLA-DR Antigens
  • Immunoglobulin A
  • Receptors, Thyrotropin