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

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.