The association of HLA-DR/DQ coding and QBP promoter allelic polymorphism with antiphospholipid antibody response in SLE

To ascertain if the polymorphism of HLA-DR, DQA and DQB alleles and QAP and QBP promoters influences the production of aCL and anti-β2-GP1 in SLE. While the role of HLA-antigens in directing various autoantibody responses is relatively well known, the effect of promoters is less established. Sixty-five consecutive unrelated Slovenian SLE patients (all female, mean age ± SD 36 ± 8.3 years, mean follow-up 93 months) and 74 unrelated healthy adults were investigated. aCL and anti-β2-GP1 were determined by ELISA. The patients and controls were typed for DRB1, DQB1, QAP and QBP alleles by PCR-SSO, using the 12th IHW primers, probes and protocols. The subtyping of DQB1 alleles as well as DQA1 typing was carried out with selected Dynal SSP primers. Allelic and deduced haplotypic frequencies in patients and controls were compared using Fisher's exact test. 32 (49%) and 16 (25%) of 65 SLE patients were positive for IgG, IgM and/or IgA aCL and anti-β2-GP1, respectively. The frequency of the DQB1*0202 allele was significantly higher in the aCL (P = 0.001) and anti-β2-GP1 (P = 0.001) negative patients than in controls. Conversely, the DQB1*0301 allele and its promoter QBP3.1 were underestimated in the aCL (P = 0.06) and anti-β2-GP1 (P = 0.001) negative patients compared with controls. The DQB1*0202 allele may have a preventive role in provoking autoimmune response against both tested aPL. While the DQB1*0301 allele and its promoter QBP3.1 were underestimated in anti-β2-GP1 negative patients, they did not seem to protect from β2-GP1 specific autoimmune response in SLE patients. In contrast, we have already observed positive correlation of anti-Ro antibody response with the DQB1*0202 allele and the significantly underestimated DQB1*0301 allele and its promoter QBP3.1 in the same group of anti-Ro positive SLE patients.