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.
Department of Medicine, University of Iceland, Reykjavík, Iceland.
Gudmundur H
GH
Jorgensen
Arni E
AE
Ornolfsson
Ari
A
Johannesson
Sveinn
S
Gudmundsson
Magdalena
M
Janzi
Ning
N
Wang
Lennart
L
Hammarström
Bjorn R
BR
Ludviksson
D000328:Adult; D000483:Alleles; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology*; D015551:Autoimmunity / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006111:Graves Disease / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007055:Iceland; D017098:IgA Deficiency / Q000235:genetics / Q000276:immunology*; D007070:Immunoglobulin A / Q000097:blood; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011863:Radioimmunoassay; D011989:Receptors, Thyrotropin / Q000235:genetics / Q000276:immunology*; D013548:Sweden
D001323:Autoantibodies; D015235:HLA-B Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D007070:Immunoglobulin A; D011989:Receptors, Thyrotropin