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

ABSTRACT

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-DRB1*150201, DRB5*010201, DQB1*050124, DPB1*130101, and DQA1*010101 were increased significantly in the whole SSc and SSc patients with positive ATA, but with negative ACA (SSc/ATA+/ACA-). Of these, DPB1*130101 was the most susceptible allele. The DRB1*150201, DQB1050124, and DPB1*130101 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 DRB1*15/16 revealed that most of the DRB1*150201 alleles were linked to DRB5*010201 or DRB5*010801N. The linkage of DRB1*160201 to DRB5*010101 was observed frequently. The associations of risk alleles with several SSc clinical features were observed. HLA-DRB1*150201, DRB5*010201, DQB1*050124, and DPB1*130101 on the unique haplotype were associated with the pathogenesis and clinical features of SSc in Thai patients. The linkage of DRB1*150201 to DRB5*010801N was observed commonly in northern Thai patients.