ESPE2018 Poster Presentations Thyroid P1 (22 abstracts)
HLA Alleles and Amino Acid Variants of HLA-A, -B, -C, -DRB1, -DQB1, -DPB1 Molecules in Early-Onset Autoimmune Thyroid Disease
Won Kyoung Cho a , Dong Hwan Shin b , Seul Ki Kim c , Seonhwa Lee d , Yujung Choi d , Moonbae Ahn d , In Cheol Baek b , Min Ho Jung c , Tai-Gyu Kim b, & Byung-Kyu Suh d
aDepartment of Pediatrics, College of Medicine, St Vincent’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea; bDepartment of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; cDepartment of Pediatrics, College of Medicine, Yeouido St Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea; dDepartment of Pediatrics, College of Medicine, Seoul St Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea; eCatholic Hematopoietic Stem Cell Bank, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
Objective: We try to investigate the polymorphisms and amino acid variants of HLA-A, -B, -C, -DRB1, -DQB1, -DPB1 molecules in early-onset AITD.
Methods: The genotypes of HLA-A, B, C, DRB1, DQB1, and DPB1 on AITD were analyzed in 102 Korean children with AITDs (Graves’ disease (GD)=62, Hashimoto’s disease (HD)=40) and 142 healthy control using sequence-based typing. Analysis of variant amino acids was performed across the genotyping results with a resolution of 4 digits from the ImMunoGeneTics database.
Results: In AITD, the allele frequencies of HLA-A * 0207, -B * 4601, -DPB1 * 0202 were higher and those of HLA- Cw * 0602, - Cw * 1403, -DRB1 * 0701, -DQB1 * 0202, -DQB1 * 0501, -DQB1 * 0604 were lower than in controls. In GD, those of HLA- -B * 4601(OR=4.0, Pc=0.005), -DPB1 * 0202(OR=4.4, Pc=0.013), -DPB1 * 0501 (OR=4.1, Pc=0.005) were higher than in controls. In HD, those of HLA-A * 0207(OR=5.6, Pc=0.005), -and -DPB1 * 0202(OR=7.2, Pc=0.0002) were higher than in controls. Between HD and GD, HLA-DPB1*0501 showed a significant difference (Pc=0.001). The risk of AITD in the presence of HLA-A*0207, -B*4601 and -C*0102 (OR=6.2, Pc=0.001) and HLA -DRB1*0803-DQB1*0601-DPB1*0202 are increased and HLA-A*3001, -B*1302 and -C*0602 (OR=0.1, P=0.003) is decreased. In analysis of amino acid variant of HLA molecules in patients with GD, Leu35 (OR=30.2, P=0.000001) and Glu55 (OR=30.2, P=0.000001) presented in both -DPB1*0202 and- DPB1*0501 increased than control. Cys99 (OR=3.6, Pc=0.019) in HLA-A molecules, Ala24 (OR=3.7, Pc=0.018), Lys66 (OR=4.0, Pc=0.0003), Arg69 (OR=3.7, Pc=0.0003), Val76 (OR=3.7, Pc=0.0002) in HLA-B molecules, Lys6 (OR=2.2, Pc=0.018), Phe9 (OR=2.2, Pc=0.035), Cys99 (OR=2.2, Pc=0.035), Tyr116 (OR=3.0, Pc=0.007) in HLA-C molecules, Ser57 (OR=3.1, Pc=0.001), Leu74 (OR=3.1, Pc=0.002) in HLA-DRB1 molecules, Asp57 (OR=15.7, Pc=0.002) in HLA-DQB1 molecules are increased in patients with GD than control.
Conclusion: Significant differences in the amino-acid signatures of HLA-molecules were observed between early-onset AITD patients and controls.
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