HLA-DQA1*0501 is associated with diffuse systemic sclerosis in Caucasian men

Area of Science:

• Immunogenetics
• Rheumatology
• Human Genetics

Background:

• Systemic sclerosis (SSc) is a rare autoimmune disease with limited understanding of its pathogenesis in men.
• Human Leukocyte Antigen (HLA) class II alleles are implicated in autoimmune diseases, but their specific role in male SSc is underexplored.

Purpose of the Study:

• To investigate HLA class II alleles (DQA1, DQB1, DRB1) in Caucasian men with SSc.
• To explore the hypothesis that maternal HLA compatibility is a risk factor for SSc in men.

Main Methods:

• Sequence-specific oligonucleotide probe typing was employed to determine HLA DQA1, DQB1, and DRB1 alleles.
• Allele frequencies were compared between SSc patients (50 men, 36 parous women) and healthy controls (59 men, 80 parous women).
• Mothers of SSc patients and healthy men were also genotyped to assess maternal HLA compatibility.

Main Results:

• The DQA1*0501 allele was significantly more frequent in men with SSc compared to healthy men (OR 2.3, P=0.006).
• DQA1*0501 was specifically associated with diffuse SSc in men (OR 3.0, P=0.004).
• No increased risk of SSc in men was associated with maternal HLA compatibility.

Conclusions:

• A specific DQA1 allele (DQA1*0501) is associated with SSc in men, potentially explaining previously observed DRB1 associations due to linkage disequilibrium.
• The genetic contribution of HLA genes to SSc risk appears substantially greater in men than in parous women.
• This study highlights sex-specific genetic factors in SSc pathogenesis.