HLA Association among Thai Patients with Diffuse and Limited Cutaneous Systemic Sclerosis

TL;DR

This study explores the link between HLA genes and two types of systemic sclerosis in Thai patients, finding different HLA associations for each disease subtype.

Contribution

The study identifies specific HLA alleles and haplotypes associated with diffuse and limited cutaneous systemic sclerosis in the Thai population.

Findings

HLA Class II alleles like DRB1*15:02:01 and DQB1*05:01:24 are significantly associated with diffuse cutaneous systemic sclerosis.

HLA Class I alleles such as A*24:02:01 and B*27:06 show a possible role in limited cutaneous systemic sclerosis.

A protective association was found for DPB1*05:01:01 in limited cutaneous systemic sclerosis.

Abstract

This study aimed to clarify the association of HLA Class I and II with dcSSc and lcSSc in Thais. HLA typing for 11 gene loci (Class I: HLA-A, B and C, and Class II [HLA-DR, DP and DQ]) was carried out using the Next Generation DNA Sequencing method (three fields) in 92 Thai patients with systemic sclerosis (55 dcSSc, 37 lcSSc) and 135 healthy controls (HCs). The distribution of HLA alleles in patients with dcSSc and lcSSc was compared. When compared with HCs, the AF of A*24:02:01, A*24:07:01, B*27:04:01 and B*27:06 showed an increasing trend in lcSSc patients without statistical significance. DRB1*15:02:01, DRB5*01:02:01, DQA1*01:01:01, DQB1*05:01:24, DPA1*02:01:01 and DPB1*13:01:01 increased significantly in dcSSc patients. DQB1*05:01:24 and DPB1*13:01:01 also increased significantly in lcSSc patients, but less significantly than in dcSSc patients. The association of DPB1*05:01:01 with lcSSc was significantly protective. HLA-A*24:02:01, B*27:06 and C*03:04:01 formed a three-locus haplotype that also constituted an eight-locus haplotype with DRB1*15:02:01, DQA1*01:01:01, DQB1*05:01:24, DPA1*02:01:01 and DPB1*13:01:01. There was a possibility that HLA Class I would play a role in the pathogenesis of lcSSc, while Class II played more of a role in the dcSSc in Thai patients.