Interactions between neutrophil extracellular traps and antiphospholipid antibodies in cancer patients

Activation of NETosis processes has been detected in numerous autoimmune and non-autoimmune diseases with increasing concentrations of antiphospholipid antibodies (APA). Neutrophil extracellular traps (NETs) are an important activator of the coagulation cascade and an integral component of arterial and venous clots in cancer patients. Therefore, APA and NETs may be the links in the pathogenesis of thrombosis in cancer patients. Objective. To evaluate the severity of NETosis, hemostatic system activation and APA circulation (anti-β2-glycoprotein 1 (anti-β2-GPI)) in cancer patients. Design. A prospective controlled interventional non-randomized study. Patients and methods. This study included 144 patients who were divided into two groups: the study group – 111 patients aged 34–72 years with malignant breast and gynecological diseases of stages I–III (endometrial cancer, n = 25; ovarian cancer, n = 36; cervical cancer, n = 17; breast cancer, n = 33), and the control group – 33 healthy women. Prior to therapy, serum concentrations of NETosis markers – citrullinated histone H3 (citH3) and human myeloperoxidase antigen (MPO:Ag), markers of hemostatic activation (D-dimer and thrombin-antithrombin complex), and anti-β2-GPI antibodies were assessed. Results. Anti-β2-GPI antibodies were significantly more common in patients with ovarian cancer compared to controls. A significant correlation between the circulation of anti-β2-GPI and the concentration of MPO:Ag was also detected in these patients. All patients in the study group showed a significant increase in the markers of NETosis and hemostatic activation compared to controls. The revealed correlation between the concentrations of NETosis markers and anti-β2-GPI antibodies in ovarian cancer suggests a possible pathogenetic role of APA in the progression of ovarian cancer and NETs-mediated prothrombotic state against the background of APA circulation. It can be assumed that APA formed in cancer patients may be one of the triggers of NETosis. NETosis itself contributes to the development of thrombotic events and stimulates further synthesis of APA. Perhaps it is the activation of NETosis that explains the worse prognosis in cancer patients with APA circulation. Conclusion. The results of this study improve the understanding of interactions between the immune and hemostatic systems. Further research is needed to determine the role of APA in NETosis, as well as the role of NETosis and APA circulation in tumor progression, metastasis, and cancer-associated thrombosis. Key words: neutrophil extracellular traps, NETosis, antiphospholipid antibodies, cancer, neutrophils, anti-β2-GPI