HLA alleles, especially amino-acid signatures of HLA-DPB1, might contribute to the molecular pathogenesis of early-onset autoimmune thyroid disease

Abstract

The major histocompatibility complex region has been suggested to play an important role in the development of autoimmune thyroid disease (AITD). In this study, we investigated the associations of human leukocyte antigen (HLA) alleles and amino acid variants of HLA with early-onset AITD. HLA class I and class II genes were analyzed in 116 Korean children with AITDs (Graves’ disease [GD]: 71, Hashimoto’s disease [HD]: 45) and 142 healthy controls. HLA-B*46:01 (OR = 3.96, Pc = 0.008), -C*01:02 (OR = 2.51 Pc = 0.04), -DPB1*02:02 (OR = 3.99, Pc = 0.04), and -DPB1*05:01 (OR = 4.6, Pc = 0.003) were significantly associated with GD, and HLA-A*02:07 (OR = 4.68, Pc = 0.045) and -DPB1*02:02 (OR = 6.57, Pc = 0.0001) with HD. The frequency of HLA-DPB1*05:01 was significantly higher in GD patients than in HD patients ( Pc = 0.0005). Furthermore, differences were found between patients with Thyroid associated ophthalmopathy (TAO) and those without TAO in the distribution of HLA-B*54:01 (8.6% vs. 30.6%, P = 0.04) and -C*03:03 (37.1% vs. 11.1%, P = 0.02). In the analysis of amino acid variants of HLA molecules, both Leu35 (OR = 23.38, P = 0.0002) and Glu55 (OR = 23.38, P = 0.0002) of HLA-DPB1 were strongly associated with GD and showed different distributions between GD and HD ( P = 0.001). Our results suggest that HLA alleles, especially amino-acid signatures of the HLA-DP β chain, might contribute to the molecular pathogenesis of early-onset AITD.

Distributions of HLA‐A, ‐B, and ‐DRB1 alleles typed by amplicon‐based next generation sequencing in Korean volunteer donors for unrelated hematopoietic stem cell transplantation

“…Genomic DNA was extracted from 4 mL of peripheral blood mixed with ethylenediaminetetraacetic acid (EDTA) using the TIANamp Genomic DNA Extraction Kits (Tiangen Biotech Corporation, Beijing, China), according to the manufacturer's instructions. Extracted DNA was adjusted to a concentration of 40 to 100 ng/μL in Tris‐ethylenediaminetetraacetic acid (TE) buffer 19 . All subjects provided informed consent to participate in the genetic study.…”

“…Extracted DNA was adjusted to a concentration of 40 to 100 ng/μL in Trisethylenediaminetetraacetic acid (TE) buffer. 19 All subjects provided informed consent to participate in the genetic study. This study protocol was approved by the Institutional Review Board (IRB) of the Catholic University of Korea (IRB Number: MC13SISI0126), Seoul, Korea, and conducted in accordance with the Declaration of Helsinki.…”

Comprehensive Analysis of CD4+ T Cell Responses to CMV pp65 Antigen Restricted by Single HLA-DR, -DQ, and -DP Allotype Within an Individual

“…PBMCs were then cryopreserved in liquid nitrogen suspended in FBS (Gibco) containing 10% dimethyl sulfoxide (Mylan) and 50% RPMI 1640 medium (Lonza). HLA typing was performed by Catholic Hematopoietic Stem Cell Bank (Seoul, Korea), using polymerase chain reaction-sequencing based typing and next-generation sequencing (MiSeq, Illumina) with genomic DNA isolated from red blood cells and granulocytes (Tiangen Biotech Corporation), as previously described ( 35 ). Research conducted for this study was approved by the Institutional Review Board of the Catholic University of Korea (MC20SESI0034).…”

GPR174 and ITM2A Gene Polymorphisms rs3827440 and rs5912838 on the X chromosome in Korean Children with Autoimmune Thyroid Disease

“…The concentration of the DNA solution was adjusted to 100 ng/μL, and the solution was stored at −20 °C. Samples were used as a polymerase chain reaction (PCR) template for genotyping [ 29 ].…”