title: Anti-beta2 glycoprotein I (beta2GPI) autoantibodies recognize an epitope on the first domain of beta2GPI.
abstract: Anticardiolipin (aCL) autoantibodies are associated with thrombosis, recurrent fetal loss, and thrombocytopenia. Only aCL found in autoimmune disease require the participation of the phospholipid binding plasma protein beta2 glycoprotein I (beta2GPI) for antibody binding and now are called anti-beta2GPI. The antigenic specificity of aCL affinity purified from 11 patients with high titers was evaluated in an effort to better understand the pathophysiology associated with aCL. Seven different recombinant domain-deleted mutants of human beta2GPI, and full length human beta2GPI (wild-type), were used in competition assays to inhibit the autoantibodies from binding to immobilized wild-type beta2GPI. Only those domain-deleted mutants that contained domain 1 inhibited the binding to immobilized wild-type beta2GPI from all of the patients. The domain-deleted mutants that contained domain 1 inhibited all aCL in a similar but not identical pattern, suggesting that these aCL recognize a similar, but distinguishable, epitope(s) present on domain 1.
authors.affiliation: La Jolla Pharmaceutical Company, San Diego, CA 92121, USA. mike.iverson@ljpc.com
authors.forename: G M
authors.initials: GM
authors.lastname: Iverson
authors.forename: E J
authors.initials: EJ
authors.lastname: Victoria
authors.forename: D M
authors.initials: DM
authors.lastname: Marquis
mesh_terms: D000595:Amino Acid Sequence; D000925:Anticoagulants / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology* / Q000302:isolation & purification; D002846:Chromatography, Affinity; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000032:analysis* / Q000737:chemistry / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D016296:Mutagenesis; D011994:Recombinant Proteins / Q000276:immunology; D017384:Sequence Deletion; D013921:Thrombocytopenia / Q000276:immunology; D013927:Thrombosis / Q000276:immunology; D053482:beta 2-Glycoprotein I
chemical_list: D000925:Anticoagulants; D001323:Autoantibodies; D000939:Epitopes; D006023:Glycoproteins; D011994:Recombinant Proteins; D053482:beta 2-Glycoprotein I