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.


CONCLUSIONS
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.
Guggenbuhl
P
P
Department of Rheumatology, University Hospital Rennes, France.
Jean
S
S
Jego
P
P
Grosbois
B
B
Chalès
G
G
Semana
G
G
Lancien
G
G
Veillard
E
E
Pawlotsky
Y
Y
Perdriger
A
A
D000328:Adult; D000368:Aged; D000483:Alleles; D004198:Disease Susceptibility; D005260:Female; D006682:HLA-DP Antigens / Q000235:genetics; D059868:HLA-DP beta-Chains; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012859:Sjogren's Syndrome / Q000235:genetics / Q000276:immunology*
D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen