IgA Anti-β2-Glycoprotein I Autoantibodies Are Associated with an Increased Risk of Thromboembolic Events in Patients with Systemic Lupus Erythematosus

Abstract

BackgroundThe clinical utility of testing for antiphospholipid antibodies (aPL) of IgA isotype remains controversial.Methodology/Principal FindingsTo address this issue, we reasoned that if IgA aPL contribute to the clinical manifestations of the antiphospholipid syndrome, then an association with thromboembolic events should manifest in patients whose only aPL is of IgA isotype. We performed a retrospective chart review of 56 patients (31 with systemic lupus erythematosus [SLE] and 25 without SLE) whose only positive aPL was IgA anti-β2-glycoprotein I (isolated IgA anti-β2GPI) and compared their clinical features with 56 individually matched control patients without any aPL. Patients with isolated IgA anti-β2GPI had a significantly increased number of thromboembolic events, as compared to controls. When patients were stratified into those with and without SLE, the association between isolated IgA anti-β2GPI and thromboembolic events persisted for patients with SLE, but was lost for those without SLE. Titers of IgA anti-β2GPI were significantly higher in SLE patients who suffered a thromboembolic event. Among patients with isolated IgA anti-β2GPI, there was an increased prevalence of diseases or morbidities involving organs of mucosal immunity (i.e., gastrointestinal system, pulmonary system, and skin).Conclusions/SignificanceThe presence of isolated IgA anti-β2GPI is associated with an increased risk of thromboembolic events, especially among patients with SLE. IgA anti-β2GPI is associated with an increased prevalence of morbidities involving organs of mucosal immunity.

Comorbidity and pathogenic links of chronic spontaneous urticaria and systemic lupus erythematosus – a systematic review

“…The number of microparticles correlated significantly with thrombin generation and thrombinanti-thrombin levels. In some studies, IgA autoantibodies to phospholipids (anti-cardiolipin) have been found to be a risk factor for thrombosis in patients with SLE [115,116], whereas others did not confirm this [114]. The lack of an increased thrombotic risk in patients with CSU, in spite of hypercoagulation, may be explained by an efficient activation of fibrinolysis and the anticoagulation system as well as the predominant extravascular activation of the coagulation cascade and location of fibrin deposition [104,117].…”

Circulating Immune Complexes of IgA Bound to Beta 2 Glycoprotein are Strongly Associated with the Occurrence of Acute Thrombotic Events

“…The epitopes recognized by the IgA aB2GPI are mainly located in the domains 4–5 of the B2GPI protein, this region being the phospholipid binding area. When cardiolipin is incorporated to B2GPI, IgA-binding epitopes are not accessible and patients only present isolated IgA aB2GPI antibodies 24, 25) .…”

Two cases of livedo vasculopathy with non‐criteria antiphospholipid antibodies

“…IgA with aCL activity from patients with APS were found to induce thrombosis in a mouse model . Several clinical studies have also demonstrated the possible association between this Ab and the development of thrombosis . Therefore, it has been proposed that IgA aCL are pathogenic in a similar manner to the thrombogenicity of IgG aCL .…”