Association of HLA-DRB1*15:02:01, DQB1*05:01:24 and DPB1*13:01:01 in Thai patients with systemic sclerosis.

HLA studies in patients with systemic sclerosis (SSc) have shown variable results. This study aimed to examine the association of HLA class I and II risk alleles in Thai SSc patients, and clarify the contribution of risk HLA alleles to the pathogenesis and clinical manifestations. Blood samples from 92 SSc patients and 135 healthy controls (HCs) were collected. Eleven loci of the HLA class I (HLA-A, B, and C) and class II (HLA-DR, DP, and DQ) genes were determined by a 3-field (6-digit) analysis using the Next Generation DNA Sequencing (NGS) method. Anti-topoisomerase-I antibodies (ATA) and anti-centromere antibodies (ACA) were identified by ELISA methods. Allele frequencies (AFs) of HLA-DRB115:02:01, DRB501:02:01, DQB105:01:24, DPB113:01:01, and DQA101:01:01 were increased significantly in the whole SSc and SSc patients with positive ATA, but with negative ACA (SSc/ATA+/ACA-). Of these, DPB113:01:01 was the most susceptible allele. The DRB115:02:01, DQB1:05:01:24, and DPB113:01:01 alleles were estimated to locate on the unique haplotype, and haplotype frequency was estimated to be significantly higher than those in the HCs (p = 0.002). The linkage analysis of DRB115/16 revealed that most of the DRB115:02:01 alleles were linked to DRB501:02:01 or DRB501:08:01N. The linkage of DRB116:02:01 to DRB501:01:01 was observed frequently. The associations of risk alleles with several SSc clinical features were observed. HLA-DRB115:02:01, DRB501:02:01, DQB105:01:24, and DPB113:01:01 on the unique haplotype were associated with the pathogenesis and clinical features of SSc in Thai patients. The linkage of DRB115:02:01 to DRB501:08:01N was observed commonly in northern Thai patients.