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Recurrent thrombotic events are a hallmark of Antiphospholipid Syndrome (APS). However, biomarkers to identify if a patient with antiphospholipid antibodies (aPL) is at higher risk to develop an arterial or a venous event are lacking. Recently, the pathogenic role of anti-high-density lipoproteins antibodies (anti-HDL) in the occurrence of cardiovascular disease (CVD) in autoimmunity has emerged. The aim of the present study was to evaluate the presence of IgG anti-HDL antibodies in a cohort of thrombotic APS patients and to investigate their association with clinical outcomes.   Methods:  Serum levels of IgG anti-HDL antibodies, total IgG, and complete aPL profile were assessed in 60 APS patients and 80 healthy donors (HDs) by immunoassays.   Results:  Higher levels of IgG anti-HDL were found in APS patients compared to HDs ( p  < 0.001), even after correcting for total IgG levels ( p  < 0.001). No associations with treatments or traditional cardiovascular risk factors, except for smoking habit ( p  < 0.0001), were found. Patients who experienced at least one arterial event ( n  = 30) had significantly higher levels of anti-HDL antibodies when compared to patients with venous thrombosis ( n  = 30,  p  = 0.046), this difference being stronger when adjusting for total IgG ( p  = 0.007). Additionally, patients tested positive for antiphosphatidylserine/prothrombin (IgG/IgM) antibodies had significantly higher levels of anti-HDL antibodies ( p  = 0.045).   Conclusions:  Increased levels of IgG anti-HDL antibodies can be found in APS, mainly in patients with arterial thrombosis, independently of aPL antibodies and traditional risk factors. These findings point to a role of anti-HDL antibodies in APS and support their use as a potential biomarker for arterial thrombotic events.

IgG Anti-high-Density Lipoproteins Antibodies Discriminate Between Arterial and Venous Events in Thrombotic Antiphospholipid Syndrome Patients