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

Area of Science:

• Immunogenetics
• Rheumatology
• Human Genetics

Background:

• Systemic sclerosis (SSc) exhibits variable Human Leukocyte Antigen (HLA) associations across populations.
• Understanding specific HLA risk alleles is crucial for elucidating SSc pathogenesis and clinical heterogeneity.

Purpose of the Study:

• To investigate the association of HLA class I and II risk alleles in Thai SSc patients.
• To determine the contribution of identified HLA risk alleles to SSc development and clinical manifestations.

Main Methods:

• Collected blood samples from 92 SSc patients and 135 healthy controls.
• Utilized Next Generation DNA Sequencing (NGS) for 3-field (6-digit) analysis of 11 HLA loci (class I and II).
• Employed ELISA for anti-topoisomerase-I antibody (ATA) and anti-centromere antibody (ACA) detection.

Main Results:

• Significantly increased allele frequencies of HLA-DRB1*15:02:01, DRB5*01:02:01, DQB1*05:01:24, DPB1*13:01:01, and DQA1*01:01:01 were observed in SSc patients, especially those with ATA+ and ACA-.
• DPB1*13:01:01 emerged as the most susceptible allele.
• A unique haplotype (DRB1*15:02:01, DQB1*05:01:24, DPB1*13:01:01) showed significantly higher frequency in SSc patients compared to controls.
• Linkage analysis revealed specific associations between DRB1*15:02:01 and DRB5*01:02:01 or DRB5*01:08:01N, and DRB1*16:02:01 with DRB5*01:01:01.
• Associations between risk alleles and clinical features of SSc were identified.

Conclusions:

• Specific HLA alleles, particularly on a unique haplotype, are significantly associated with SSc pathogenesis and clinical features in Thai patients.
• The identified HLA alleles contribute to understanding the genetic susceptibility and disease mechanisms in SSc.
• Linkage patterns provide further insight into the genetic architecture of HLA associations in SSc.