Anti-beta2-glycoprotein I antibodies recognizing platelet factor 4-heparin complex in antiphospholipid syndrome in patient substantiated with mouse model |
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Authors: | Bourhim Mustapha Darnige Luc Legallais Cécile Arvieux Josiane Cevallos Ramiro Pouplard Claire Vijayalakshmi Mookambeswaran A |
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Affiliation: | Laboratoire d'Interactions Moléculaires et Technologie de Séparation, Université de Technologie de Compiègne, 60205 Compiègne, France. |
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Abstract: | The antiphospholipid syndrome is defined by the presence of antiphospholipid antibodies associated with arterial and/or venous thrombosis, and recurrent abortion accompanied often by thrombocytopenia. These antibodies are heterogeneous and react against phospholipid-binding proteins such as beta2-glycoprotein I (beta2GPI) and prothrombin. The recognition of anti-beta2-glycoprotein I (anti-beta2GPI) by platelet factor 4-heparin complex (PF4-Hc) has been previously evoked and partially confirmed by the present inhibition studies. Further, the anti-beta2-glycoprotein I antibodies were purified from a patient with primary antiphospholipid syndrome using Affi-gel-10-beta2GPI immunoaffinity chromatography. The purified anti-beta2GPI IgM as well as patient serum equally recognized PF4-Hc in ELISA mode. In order to substantiate this data and to better understand we studied an animal model using mouse active immunization with the purified human anti-beta2GPI. The mice showed a significant decrease in their platelet count. In addition the ELISA responses of the immunized mice sera were positive against both beta2GPI and PF4-Hc, substantiating the double recognition. Despite many previous reported animal model studies, this is the first time we have shown the specific recognition of anti-beta2GPI antibodies by PF4-Hc, the results in the induced mice correlating the data observed with some patients. |
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Keywords: | antiphospholipid antibodies antiphospholipid syndrome β2-glycoprotein I platelet factor 4–heparin complex heparin anticardiolipin crossreactivity thrombocytopenia heparin-induced thrombocytopenia animal model |
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