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

Area of Science:

• Immunogenetics
• Rheumatology
• Human Genetics

Background:

• Systemic Sclerosis (SSc) is a complex autoimmune disease with significant genetic components.
• Human Leukocyte Antigen (HLA) genes are crucial for immune regulation and have been implicated in various autoimmune disorders.
• Previous studies suggest HLA associations with SSc, but specific roles in different subtypes and ethnic groups require further clarification.

Purpose of the Study:

• To investigate the association of HLA Class I and Class II alleles with diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc) in a Thai population.
• To identify specific HLA alleles and haplotypes linked to SSc pathogenesis in Thai patients.

Main Methods:

• HLA typing for 11 gene loci (HLA-A, B, C, DR, DP, DQ) was performed using Next Generation DNA Sequencing.
• Genotyping was conducted on 92 Thai SSc patients (55 dcSSc, 37 lcSSc) and 135 healthy controls.
• Allele frequencies (AF) were compared between patient subgroups and controls to determine significant associations.

Main Results:

• Significant associations were observed between specific HLA Class II alleles (e.g., DRB1*15:02:01, DQB1*05:01:24, DPB1*13:01:01) and dcSSc.
• HLA Class II alleles DQB1*05:01:24 and DPB1*13:01:01 were also significantly increased in lcSSc patients.
• A protective association was found for DPB1*05:01:01 in lcSSc patients.
• Trends for increased HLA Class I alleles (e.g., A*24:02:01, B*27:04:01) were noted in lcSSc patients, though not statistically significant.
• Identified multi-locus haplotypes involving both HLA Class I and Class II alleles.

Conclusions:

• HLA Class II alleles show a stronger association with the pathogenesis of dcSSc in Thai patients.
• HLA Class I alleles may contribute to the pathogenesis of lcSSc in this population.
• Specific HLA alleles and haplotypes represent potential genetic markers for SSc subtypes in Thais.