Objective: Primary antiphospholipid syndrome (APS) is formally classified by the presence of antiphospholipid antibodies, recurrent thrombosis, and/or pregnancy morbidity in the absence of any underlying full-blown systemic autoimmune disease. However, systemic manifestations in patients with primary APS have been recently reported, as has the presence of serologic markers in common with systemic lupus erythematosus (SLE). In spite of similarities between the 2 diseases, only a minority of cases of primary APS evolve into full-blown SLE, even after a long followup period. The aim of this study was to investigate whether the analysis of SLE susceptibility genes may provide at least a partial explanation for such a discrepancy.
Methods: One hundred thirty-three patients with primary APS classified according to the Sydney criteria and 468 healthy control subjects from the same geographic area were recruited. We genotyped 3 single-nucleotide polymorphisms (SNPs) in IRF5 (rs2004640, rs2070197, and rs10954213), 4 SNPs in STAT4 (rs1467199, rs3821236, rs3024866, and rs7574865), 2 SNPs in BANK1 (rs10516487 and rs3733197), and 1 SNP in BLK (rs2736340).
Results: STAT4 and BLK displayed a strong genetic association with primary APS (for rs7574865, odds ratio [OR] 2.19, P=5.17x10(-7); for rs2736340, OR 2.06, P=1.78x10(-6)), while a weak association with IRF5 and no association with BANK1 were observed.
Conclusion: The presence of a strong genetic association with only a few SLE susceptibility genes and the absence of a more complex gene association may contribute to the lack of cases of full-blown SLE developing in patients with primary APS, in spite of the clinical and serologic similarities between SLE and primary APS.