Association of IgA antiphospholipid antibodies with hypercoagulability and inflammation in antiphospholipid syndrome

Abstract Although IgA isotype testing does not enhance diagnostic accuracy of antiphospholipid syndrome (APS), recent studies suggest that IgA aCL/aβ2GPI are associated with systemic lupus erythematosus (SLE) and thrombosis, contributing to thromboinflammatory responses and potentially serving as prognostic markers. This study’s objective is to determine whether IgA aCL/aβ2GPI are associated with coagulation and inflammatory responses, as well as a high-risk thrombotic APS (t-APS) profile. A total of 81 patients with t-APS were included. IgA aCL and IgA aβ2GPI were measured using chemiluminescence. Coagulation and inflammatory markers (TNF-α, IL-6, IL-8, IFN-α, TF, VWF, ADAMTS13) were measured by ELISA, and then, their levels and activity compared between IgA-positive and negative patients. The association of IgA and relevant outcomes (antiphospholipid [aPL] profile, recurrent thrombosis, SLE), was assessed by logistic models adjusted for age and sex. IgA aCL or aβ2GPI positivity was observed in 24 patients (29.6%), mostly with both antibodies ( n = 23). IgA positivity was not associated with demographics, comorbidities or pregnancy complications, but correlated with triple aPL positivity (48% vs. 13%, P = 0.004) and higher risk of progression to SLE (17% vs. 0%, P = 0.004). IgA-positive patients showed significantly elevated TNF-α, IL-8, and TF levels ( P = 0.03, P = 0.03 and P = 0.05, respectively). In conclusion, IgA aCL/aβ2GPI positivity is associated with triple aPL positivity, progression to SLE, and altered thromboinflammatory markers, thus highlighting their association with a pronounced thromboinflammatory APS profile. This emphasizes the association of IgA antibodies with a high-risk serological profile and the potential utility of IgA testing in APS. Clinical trial registration: This study is not a clinical trial that requires registration. Graphical abstract