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

The clinical utility of testing for antiphospholipid antibodies (aPL) of IgA isotype remains controversial.To 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-beta2-glycoprotein I (isolated IgA anti-beta2GPI) and compared their clinical features with 56 individually matched control patients without any aPL. Patients with isolated IgA anti-beta2GPI 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-beta2GPI and thromboembolic events persisted for patients with SLE, but was lost for those without SLE. Titers of IgA anti-beta2GPI were significantly higher in SLE patients who suffered a thromboembolic event. Among patients with isolated IgA anti-beta2GPI, there was an increased prevalence of diseases or morbidities involving organs of mucosal immunity (i.e., gastrointestinal system, pulmonary system, and skin).The presence of isolated IgA anti-beta2GPI is associated with an increased risk of thromboembolic events, especially among patients with SLE. IgA anti-beta2GPI is associated with an increased prevalence of morbidities involving organs of mucosal immunity

High IgA antiphospholipid autoantibodies in healthy Sudanese explain the increased prevalence among Sudanese compared to Swedish systemic lupus erythematosus patients

Objectives: IgA antiphospholipid antibodies (aPL) are prevalent in systemic lupus erythematosus (SLE) patients of African American, Afro-Caribbean and South African origin. Nevertheless, data from North Africa are lacking, and most studies use manufacturer-suggested cut-offs based on Caucasian controls. Therefore, we compared aPL isotypes in Sudanese and Swedish SLE patients using nation-based cut-offs. Methods: Consecutive SLE patients and age- and sex-matched controls from Sudan (N = 115/106) and Sweden (N = 340/318) were included. All patients fulfilled the 1982 American College of Rheumatology SLE classification criteria. Antiphospholipid syndrome-related events were obtained from patients' records. IgA/G/M anticardiolipin and anti-beta(2) glycoprotein I (beta(2) GPI) were analysed with two independent assays. IgA anti-beta(2) GPI domain 1 (D1) was also investigated. Manufacturers' cut-offs and the 95th and 99th percentile cut-offs based on national controls were used. Results: Sudanese patients and controls had higher levels and were more often positive for IgA aPL than Swedes when using manufacturers' cut-offs. In contrast, using national cut-offs, the increase in IgA aPL among Sudanese patients was lost. Occurrence of IgA anti-D1 did not differ between the countries. Venous thromboses were less common among Sudanese patients and did not associate with aPL. No clinical associations were observed with IgA anti-beta(2) GPI in Sudanese patients. Thromboses in Swedes were associated with IgG/M aPL. Fetal loss was associated with aPL in both cohorts. Conclusions: IgA anti-beta(2) GPI prevalence was higher among Sudanese compared to Swedish patients when manufacturers' cut-offs were used. This situation was reversed when applying national cut-offs. Anti-D1 was not increased in Sudanese patients. Previous studies on populations of African origin, which demonstrate a high prevalence of IgA aPL positivity, should be re-evaluated using a similar cut-off approach