{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T01:25:58Z","timestamp":1788830758852,"version":"build-2803163510"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Antiphospholipid syndrome (APS) is an autoimmune condition characterized by recurrent thrombosis, pregnancy-related complications and circulating antiphospholipid antibodies, including anti-\u03b22-glycoprotein I (\u03b22-GPI). Platelet factor 4 (PF4) is a pro-coagulant protein expressed by activated platelets. It is considered a potential platelet ligand for oxidized \u03b22-GPI, and this interaction may play a role in the thrombotic manifestations of APS. This study aims to assess \u03b22-GPI\/PF4 complex autoantibodies in sera of thrombotic patients with APS and their potential functional role in platelet activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analysed sera from 73 patients with thrombotic APS, 20 with obstetric APS, 20 with systemic lupus erythematosus (SLE), 20 with non-APS thrombosis, 3 with vaccine-induced immune thrombotic thrombocytopenia (VITT), 20 with COVID-19 and 45 healthy donors (HDs). These samples were tested by ELISA for antibodies to the \u03b22-GPI\/PF4 complex after\n                      <jats:italic>in vitro<\/jats:italic>\n                      induction of spontaneous \u03b22-GPI protein oxidation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Anti-\u03b22-GPI\/PF4 were detected in 34.24% of thrombotic APS patients and 20% of obstetric APS. All VITT and none of the SLE, non-APS thrombosis, COVID-19 patients and HDs were positive for anti-\u03b22-GPI\/PF4. In thrombotic APS, a significant association was found between anti-\u03b22-GPI\/PF4 positivity and antibody titer with venous thrombotic complications (p = 0.032, p = 0.01) as well as between anti-\u03b22-GPI\/PF4 and triple positivity to conventional aPLs (p = 0.028). Notably, antibody titer correlated with the young age both at diagnosis (p&amp;lt;0.001) and at the current evaluation (p=0.001). Moreover, HDs\u2019 platelets,\n                      <jats:italic>in\u00a0vitro<\/jats:italic>\n                      treated with Ig fractions from APS patients, exhibited a significant increase in phospho-ERK and phospho-p38 expression, leading to NF-\u03baB activation and TF expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study demonstrated the presence of anti-\u03b22-GPI\/PF4 in patients with APS, where it may be involved in the mechanism underlying the hypercoagulable state and correlated with a greater risk of developing thrombosis, especially in the young population.<\/jats:p>\n                  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