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J Clin Endocrinol Metab. 2018 Dec 26. doi: 10.1210/jc.2018-01621. [Epub ahead of print]

HLA-DQB1 pos. 57 defines susceptibility to isolated and polyglandular autoimmunity in adults: interaction with gender.

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Department of Internal Medicine I, Division of Endocrinology, Diabetes and Metabolism, University Hospital Frankfurt, Germany.
Institute of Transfusion Medicine and Immunohematology, Department of Transplantation Immunology and Immunogenetics, University Hospital Frankfurt, Germany.



Autoimmune endocrinopathies result from environmental triggers on the genetic background of risk alleles, especially HLA-DR and HLA-DQ with Ala in HLA-DQB1 position 57 (Ala57), whereas amino acid Asp57 is protective.


Differentiate the effects of HLA-DQB1 amino acid variants at position 57 in adult patients with isolated endocrinopathies and autoimmune polyglandular syndrome type 2 (APS-2) compared to healthy controls (HC) in relation to gender.


University hospital Frankfurt a. Main, Germany.


278 APS-2 patients and 1373 patients with isolated endocrinopathies: (Type 1 Diabetes (T1D, n=867), Addison´s disease (AD, n=185), autoimmune thyroiditis (AIT, n=321) and 526 HC.


Homozygous HLA-DQB1 Ala57 was more frequent in polyglandular T1D/AIT (OR 11.7, pc=3x10-7) and AD/AIT (OR 4.0, pc=3x10-7), as well as in isolated T1D (OR 9.7, pc=3x10-7) and AD (OR 3.1, pc=3x10-7). Heterozygous HLA-DQB1 57 Ala/non-Ala was increased in females with isolated AD and polyglandular AD/AIT (both OR 1.7, pc=0.02) while the same amino acid variant was overrepresented in T1D men compared to women (OR 1.6, pc=0.004). The amino acid Ala57 was more frequent (OR 2.0, pc=0.02) and the amino acid Asp57 was much rarer (OR 0.4, pc=0.007) in the APS-2 cohort T1D/AIT than in AD/AIT.


HLA-DQB1 confers strong susceptibility by Ala57 homozygosity and protection by non-Ala57, both in adult isolated and polyglandular diseases. Frequencies of HLA-DQB1 amino acids differentiate between APS-2 T1D/AIT and AD/AIT. HLA-DQB1 Ala57 heterozygous women are at increased risk for AD or AIT, while males were found to have an increased susceptibility for T1D.


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