Purpose Emerging evidence demonstrate that anti-phosphatidylserine/prothrombin complex antibodies (anti-PS/PT) associate with thrombotic events. Genetic predisposition, including HLA-DRB1 alleles, is known to contribute to the occurrence of conventional antiphospholipid antibodies (aPL, anti-beta2glycoprotein-I (beta2GPI) and anti-cardiolipin (CL)). We investigated associations between anti-PS/PT and HLA-DRB1* alleles and thrombosis in SLE. Conventional aPL were included for comparison.
Methods We included 341 consecutive SLE patients, with information on general cardiovascular risk factors, including blood lipids, lupus anticoagulant and thrombotic events. Anti-PS/PT, anti-beta2GPI and anti-CL of IgA/G/M isotypes and lupus anticoagulant were quantified.
Results Anti-PS/PT antibodies associated positively with HLA-DRB1*13 (OR 2.7, P=0.002), whereas anti-beta2GPI and anti-CL antibodies associated primarily with HLA-DRB1*04 (OR 2.5, P=0.0005). These associations remained after adjustment for age, gender and other HLA-DRB1* alleles. HLA-DRB1*13, but not DRB1*04, remained as an independent risk factor for thrombosis and APS, after adjustment for aPL and cardiovascular risk factors. The association between DRB1*13 and thrombosis was mediated by anti-PS/PT positivity. HLA-DRB1*03, on the other hand, associated negatively with thrombotic events as well as all aPL using both uni- and multi-variate analyses. HLA-DRB1*03 had thrombo-protective effect in aPL positive patients. Additionally, HLA-DRB1*03 was associated with a favorable lipid profile regarding high-density lipoprotein and triglycerides.
Conclusions HLA-DRB1*13 confers risk for both anti-PS/PT and thrombotic events in lupus. The association between HLA-DRB1*13 and thrombosis is largely, but not totally, mediated through anti-PS/PT. HLA-DRB1*03 was negatively associated with aPL and positively with favorable lipid levels. Thus, HLA-DRB1*03 seems to identify a subgroup of SLE patients with reduced vascular risk.
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