title: Anti-beta2-glycoprotein I antibodies recognizing platelet factor 4-heparin complex in antiphospholipid syndrome in patient substantiated with mouse model.
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.
authors.affiliation: Laboratoire d'Interactions Moléculaires et Technologie de Séparation, Université de Technologie de Compiègne, 60205 Compiègne, France.
authors.forename: Mustapha
authors.initials: M
authors.lastname: Bourhim
authors.forename: Luc
authors.initials: L
authors.lastname: Darnige
authors.forename: Cécile
authors.initials: C
authors.lastname: Legallais
authors.forename: Josiane
authors.initials: J
authors.lastname: Arvieux
authors.forename: Ramiro
authors.initials: R
authors.lastname: Cevallos
authors.forename: Claire
authors.initials: C
authors.lastname: Pouplard
authors.forename: Mookambeswaran A
authors.initials: MA
authors.lastname: Vijayalakshmi
mesh_terms: D000328:Adult; D000818:Animals; D000906:Antibodies / Q000276:immunology* / Q000302:isolation & purification; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000276:immunology* / Q000473:pathology; D003429:Cross Reactions; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000097:blood / Q000276:immunology*; D006493:Heparin / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D008081:Liposomes; D051379:Mice; D010976:Platelet Count; D010978:Platelet Factor 4 / Q000276:immunology* / Q000378:metabolism; D011247:Pregnancy; D053482:beta 2-Glycoprotein I
chemical_list: D000906:Antibodies; D006023:Glycoproteins; D007075:Immunoglobulin M; D008081:Liposomes; D053482:beta 2-Glycoprotein I; D010978:Platelet Factor 4; D006493:Heparin