Anna U Kraus1, Marissa Penna-Martinez1, Firouzeh Shoghi1, Christian Seidl2, Gesine Meyer1, Klaus Badenhoop1. 1. Department of Internal Medicine I, Division of Endocrinology, Diabetes and Metabolism, University Hospital Frankfurt, Frankfurt, Germany. 2. Institute of Transfusion Medicine and Immunohematology, Department of Transplantation Immunology and Immunogenetics, University Hospital Frankfurt, Frankfurt, Germany.
Abstract
CONTEXT: Autoimmune endocrinopathies result from environmental triggers on the genetic background of risk alleles, especially HLA-DR and HLA-DQ with alanine (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 with healthy controls in relation to gender. SETTING: University Hospital Frankfurt, Frankfurt, Germany. PARTICIPANTS: Two hundred seventy-eight patients with APS-2 and 1373 patients with isolated endocrinopathies: [type 1 diabetes (T1D), n = 867], Addison disease (AD, n = 185), autoimmune thyroiditis (AIT, n = 321) and 526 healthy controls. RESULTS: Homozygous HLA-DQB1 Ala57 was more frequent in polyglandular T1D/AIT (OR 11.7, Pc = 3 × 10-7) and AD/AIT (OR 4.0, Pc = 3 × 10-7), as well as in isolated T1D (OR 9.7, Pc = 3 × 10-7) and AD (OR 3.1, Pc = 3 × 10-7). Heterozygous HLA-DQB1 57 Ala/non-Ala was increased in women with isolated AD and polyglandular AD/AIT (both OR 1.7, Pc= 0.02) whereas the same amino acid variant was overrepresented in men with T1D compared with 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 more rare (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, whereas men were found to have an increased susceptibility for T1D.
CONTEXT: Autoimmune endocrinopathies result from environmental triggers on the genetic background of risk alleles, especially HLA-DR and HLA-DQ with alanine (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 with healthy controls in relation to gender. SETTING: University Hospital Frankfurt, Frankfurt, Germany. PARTICIPANTS: Two hundred seventy-eight patients with APS-2 and 1373 patients with isolated endocrinopathies: [type 1 diabetes (T1D), n = 867], Addison disease (AD, n = 185), autoimmune thyroiditis (AIT, n = 321) and 526 healthy controls. RESULTS: Homozygous HLA-DQB1Ala57 was more frequent in polyglandular T1D/AIT (OR 11.7, Pc = 3 × 10-7) and AD/AIT (OR 4.0, Pc = 3 × 10-7), as well as in isolated T1D (OR 9.7, Pc = 3 × 10-7) and AD (OR 3.1, Pc = 3 × 10-7). Heterozygous HLA-DQB1 57 Ala/non-Ala was increased in women with isolated AD and polyglandular AD/AIT (both OR 1.7, Pc= 0.02) whereas the same amino acid variant was overrepresented in men with T1D compared with 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 more rare (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-DQB1Ala57 heterozygous women are at increased risk for AD or AIT, whereas men were found to have an increased susceptibility for T1D.
Authors: Anna U Kraus; Marissa Penna-Martinez; Firouzeh Shoghi; Gesine Meyer; Klaus Badenhoop Journal: Front Immunol Date: 2020-12-07 Impact factor: 7.561