Augmented oxidative stress, accumulation of DNA damage and impaired DNA repair mechanisms in thrombotic primary antiphospholipid syndrome

Antiphospholipid syndrome (APS) is a rare autoimmune disorder with complex pathogenesis. Studies have shown that oxidative stress may contribute to APS pathophysiology. In peripheral blood mononuclear cells (PBMCs) from thrombotic Primary APS (thrPAPS) patients and age/sex-matched healthy controls (HC), as well as a control group of asymptomatic antiphospholipid antibody (aPL) positive individuals without APS (aPL+/nonAPS), we examined oxidative stress, abasic (apurinic/apyrimidinic) sites, and DNA damage response (DDR)associated parameters, including endogenous DNA damage (single- and double-strand breaks) and DNA repair mechanisms, namely nucleotide excision repair (NER) and double-strand breaks repair (DSB/R). We found that thrPAPS patients exhibited significantly higher levels of endogenous DNA damage, increased oxidative stress and abasic sites, as well as lower NER and DSB/R capacities versus HC (all P < 0.001) and versus aPL+/non-APS subjects (all P < 0.05). Our findings demonstrate that oxidative stress and decreased DNA repair mechanisms contribute to the accumulation of endogenous DNA damage in PBMCs from thrPAPS patients and, if further validated, may be exploited as therapeutic targets and potential biomarkers.

Automated summary

Antiphospholipid syndrome (APS) is a rare autoimmune disorder characterized by oxidative stress and decreased DNA repair mechanisms, leading to the accumulation of endogenous DNA damage. In this study, thrombotic primary APS (thrPAPS) patients showed significantly higher levels of endogenous DNA damage, increased oxidative stress, and abasic sites, as well as lower nucleotide excision repair (NER) and double-strand breaks repair (DSB/R) capacities compared to healthy controls and asymptomatic antiphospholipid antibody (aPL) positive individuals without APS. These findings suggest that oxidative stress and impaired DNA repair may serve as potential therapeutic targets and biomarkers for APS.