The persistence of anticardiolipin antibodies is associated with an increased risk of the presence of lupus anticoagulant and anti-β2-glycoprotein I antibodies

The presence of antiphospholipid antibodies (aPL) has been shown to be associated with arterial (AT) and venous thrombosis (VT) [1]. However, thrombosis does not occur in all aPL-positive individuals, and predicting which patients may develop thrombotic events remains one of the major clinical dilemmas in this area. Hence, it would be of tremendous clinical value to determine serological markers or tests that can identify patients at high risk of thrombosis. Persistence of anticardiolipin antibody (aCL) positivity has been shown to be of diagnostic importance in identifying systemic lupus erythematosus (SLE) patients at higher risk of thrombosis [2, 3]. aCL persistence has also been associated with a higher incidence of lupus anticoagulant (LA) [3]. Multiple different aPL [e.g. LA, anti-β2-glycoprotein I antibodies (aβ2GPI) and antiprothrombin] are often present in an individual with aCL, but the diagnostic utility of aPL other than aCL and LA remains questionable [4–6]. Other retrospective studies have shown that individuals with more than one aPL are at greater risk of thrombosis than those with a single aPL [7–12]. The mechanism responsible for the development of these multiple aPL remains unknown, but epitope spreading is one potential mechanism that can explain the presence of multiple and related autoantibodies in a given individual [13]. In fact, in patients with SLE, aPL (specifically, aCL) have been shown to precede the development of other autoantibodies and to precede the development of disease by 7 or 8 yr [13]. We propose that autoantibodies in patients with antiphospholipid syndrome also develop and emerge in an ordered pattern, and that clinical symptoms may occur only after multiple autoantibodies have been present for several to many years. In the present study, we were interested in exploring whether the persistent presence of aCL is associated with an increased risk of the development of other aPL. In particular, we focused on whether persistent aCL positivity is associated with an increased risk of the presence of LA and anti-β2GPI antibodies, and evidence for a temporal relationship in the development of these different aPL. Such an association might provide better diagnostic criteria for identifying patients at risk of thrombosis, and a better understanding of the development and pathogenesis of aPL.