Introduction: 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.