HLA markers and clinical characteristics in Caucasians with primary Sjögren's syndrome.
OBJECTIVE
To explore the association between HLA genotypes and clinical and immunological characteristics in Caucasians with primary Sjögren's syndrome (pSS).


METHODS
HLA genotyping for DRB1, DQA1 and DQB1 was carried out in 62 single case patients with pSS and 64 healthy controls. The specific amino acid residues at DQA1 position 34 (DQalpha-34Q) and DQB1 position 26 (DQbeta-26L) in addition to the DQ-DI (AA59-AA69) motif were deterrmined. Subsequently, the relative contribution of individual HLA markers to clinical and immunologic characteristics of pSS was assessed by group comparisons.


RESULTS
No significant associations were seen between HLA markers and histopathological or clinical features of pSS. Significant positive associations with HLA Class II markers were restricted to the formation of different autoantibodies. Formation of an anti-Ro/SSA and anti-La/SSB autoantibody response was positively associated with DRB1*03, DQB1*02 and DRB1*03/DRB1*15-DQB1*02/DQB1*0602 heterozygosity. Patients positive for anti-La/SSB also showed a strong positive anti-La/SSB association with DQA1*0501. Considering the contribution of individual DQA1 and DQB1 amino acids and sequence motifs to the formation of anti-Ro/SSA and anti-La/SSB autoantibodies, a dose dependent positive influence was detected for DQalpha-34Q and DQbeta-26L. For DQbeta-DI, the largest difference between patients and controls was seen for the presence of a single copy of this motif after selecting patients with either anti-Ro/SSA or anti-La/SSB autoantibodies.


CONCLUSIONS
The association of HLA Class II markers with pSS may concern the anti-Ro/La response rather than the disease itself. The strongest contributors to the formation of an anti-Ro/La response included components of the DRB1*03-DQB1*02-DQA1*0501 haplotype also encompassing the transethnically-associated DQbeta-DI motif. In addition, the dose dependent contribution of DQalpha-34Q and DQbeta-26L argue for a recessive contribution of HLA-DQ to the formation of an anti-Ro/La response. Given the prominent associations with DRB1*03 and the complex dose dependent interactions at HLA-DQ, a joint contribution of HLA-DR and DQ is likely to be relevant for the formation of anti-Ro/La autoantibodies in patients with pSS.
Bolstad
A I
AI
Broegelmann Research Laboratory, University of Bergen, Germany.
Wassmuth
R
R
Haga
H J
HJ
Jonsson
R
R
D000974:Antibodies, Antinuclear / Q000097:blood; D001324:Autoantigens / Q000276:immunology; D015415:Biomarkers; D005260:Female; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D012261:Ribonucleoproteins / Q000276:immunology; D012859:Sjogren's Syndrome / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D044465:White People; D000097585:SS-B Antigen
D000974:Antibodies, Antinuclear; D001324:Autoantigens; D015415:Biomarkers; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D012261:Ribonucleoproteins; D000097585:SS-B Antigen; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; C035356:SS-A antibodies