While IgA anticardiolipin (aCL) and anti-β2 Glycoprotein 1 (aβ2GPI) testing doesn't enhance Antiphospholipid Syndrome (APS) diagnostic accuracy, their prognostic role remains nuclear. Recent research suggests IgA-immune complexes can trigger thromboinflammatory responses, linking them to SLE diagnosis and thrombosis risk.

This study investigated if IgA positivity for aCL or aβ2GPI associates with high-risk thrombotic APS patients, potentially serving as a prognostic marker.

We assessed IgA positivity in 81 thrombotic APS patients at the University of Campinas (1990‒2015). Exclusion criteria were no diagnostic criteria for APS, concomitant systemic autoimmune diseases and no history of thrombosis.

A total of 81 patients were included, 72.8% women and 27,2% men. 56 had venous and 25 arterial thrombosis. 41,9% of the patients had secondary APS, mostly due to systemic lupus erythematous (SLE) and 20,9% had triple positivity for aPL. Overall, 24 patients (29.6%) were positive for IgA aCL (n = 15) or aβ2GPI (n = 23). IgA positivity was not associated with demographic and clinical characteristics. Venous thrombosis was the index thrombotic event in IgA-positive patients (n = 20), compared to IgA-negative patients (p=0.06). Recurrent thrombosis was similar between the groups (p = 0.25). While IgA positivity didn't correlate with secondary APS at diagnosis, progression to SLE was associated with IgA-positivity (OR=43.8, 95% CI 2.1‒902, p=0.004). Also, IgA positive patients were 6 times more likely to be triple positive for aPL than IgA negative patients (OR=6.2, 95% CI 1.9‒20). IgA-positive patients showed increased coagulation and inflammation, with significantly higher levels of TF (aCL R = 0.26, aB2GP1 R = 0.27; p = 0.05), IL-8 (aCL R = 0.3, aB2GP1 R = 0.29; p = 0.03), and TNF-alpha (aCL R = 0.24, aB2GP1 R = 0.29; p = 0.03). FVW, IL-6, INF-α and ADAMTS-13 levels were similar between IgA-positive and -negative patients.

In the present cohort, we observed a higher frequency of triple positivity in patients with positive IgA aCL or aB2GP1 in relation to patients with negative IgA. This suggests that testing for these specific IgA antibodies could serve as a substitute for standard diagnostic tests, especially when triple positivity testing isn't possible (for ex., in anticoagulated patients). The study showed a tendency toward more venous manifestations. Most notably, patients with positive IgA antibodies had a higher risk of developing SLE during follow-up, which suggests that detecting these antibodies could be useful for monitoring patients and watching for signs of SLE. Additionally, IgA-positive patients also demonstrated activation of coagulation and inflammation, with significant increases in TF, IL-8 and TNF-alpha levels. Our findings highlight that IgA antibodies are associated with a more inflammatory and hypercoagulable profile of APS, and could be used as a prognostic marker. The study's limitations include its retrospective design and the fact that the IgA antibodies were tested only once, without a follow-up test to confirm their persistence. In conclusion, our results showed that positive IgA-class antibodies are associated with triple positivity of aPL, increased inflammation and hypercoagulability state, which could reveal a reserved disease prognosis.