A novel mechanism of thrombosis in antiphospholipid antibody syndrome

Journal of Autoimmunity
Panayiotis G Vlachoyiannopoulos, John G Routsias

Abstract

Antiphospholipid antibody syndrome (APS) is an autoimmune thrombophilia mediated by autoantibodies directed against phospholipid-binding plasma proteins, mainly β2 Glycoprotein I (β2GPI)-a plasma apolipoprotein and prothrombin (PT). A subgroup of these antibodies termed "Lupus Anticoagulant" (LA) elongate in vitro the clotting times, this elongation not corrected by adding normal plasma in the detection system. The exact mechanism by which these autoantibodies induce thrombosis is not well understood. Resistance to natural anticoagulants such as protein C, impaired fibrinolysis, activation of endothelial cells to a pro-coagulant phenotype and activation of platelets, are among the mechanisms partially supported by experimental evidence. Artificially dimerized β2GPI binds tightly to platelet membrane activating them. We search for mechanisms of natural dimerization of β2GPI by proteins of the platelet membranes and found that platelet factor 4 (PF4) assembled in homotetramers binds two molecules of β2GPI and this complex is recognized by anti-β2GPI antibodies, the whole complexes being thrombogenic in terms of activating platelets as confirmed by p38MAP kinase phosphorylation and thromboxane B2 production. Of note PF4/heparin co...Continue Reading

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Citations

Sep 1, 2014·Journal of the Neurological Sciences·De-Sheng ZhuQiang Dong
Aug 7, 2012·Journal of Autoimmunity·Christophe JaminJacques-Olivier Pers
Jul 4, 2012·Journal of Autoimmunity·Manuel J Amador-PatarroyoJuan-Manuel Anaya
Mar 1, 2012·Journal of Autoimmunity·A G Tzioufas, P G Vlachoyiannopoulos
May 31, 2011·Journal of Autoimmunity·M Eric Gershwin, Yehuda Shoenfeld
Jul 19, 2011·Autoimmunity Reviews·Carlo Selmi
May 7, 2011·Autoimmunity Reviews·Cristiano AlessandriGuido Valesini
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Apr 4, 2021·Journal of Clinical Medicine·Takako Miyamae, Tomohiro Kawabe

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