Primary Sjögren's Syndrome: Role of the HLA-DRB1*0301-*1501 Heterozygotes

Objective: To examine the respective role of the DRB1*, DQB1*, and DPB1* HLA alleles in primary Sjögren's syndrome (SS) and in the clinical and autoantibody profile of primary SS.

Methods: HLA-DRB1*, DQB1*, and DPB1* alleles were analyzed in 42 patients with primary SS and 200 controls by reverse dot blot hybridization for DRB1* and DPB1* and by polymerase chain reaction-restriction fragment length polymorphism for DQB1*.

Results: We found a significant increase of the HLA-DRB1*15-*03 heterozygote genotype frequency (19% primary SS vs 3.5% controls; p<0.0006, OR=6.49) and especially for the HLA-DRBI*1501-*0301 genotype (16.7% primary SS vs 3% controls; p<0.002, OR=6.47). The DQB1*0201-*0602 genotype was also significantly increased in primary SS (17.1% primary SS vs 4% controls; p<0.006, OR=4.86). However, the higher risk to primary SS development was associated with the DRB1*1501-*0301 genotype (OR=6.47 vs 4.86). There were no differences between patients and controls in DPB1* allele frequencies. The HLA-DRB1*15-*03 heterozygote genotype was also associated with systemic features such as hematologic manifestations and Raynaud's phenomenon (RP) and with autoantibody production such as antinuclear, anti-Ro(SSA) or La(SSB) autoantibodies and rheumatoid factor.

Conclusion: Our data suggest a role of the HLA-DRB1*1501-*0301 heterozygote genotype in susceptibility to primary SS. Moreover, the HLA-DRB1*1501-*0301 genotype was also found to be associated with a particular form of the disease characterized by RP, hematologic manifestations, and autoantibody production.