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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.

Author information

1
Department of Internal Medicine I, Division of Endocrinology, Diabetes and Metabolism, University Hospital Frankfurt, Germany.
2
Institute of Transfusion Medicine and Immunohematology, Department of Transplantation Immunology and Immunogenetics, University Hospital Frankfurt, Germany.

Abstract

Context:

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.

Objectives:

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.

Setting:

University hospital Frankfurt a. Main, Germany.

Participants:

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.

Results:

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.

Conclusion:

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.

PMID:
30590628
DOI:
10.1210/jc.2018-01621

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