Anti-beta2 glycoprotein I (beta2GPI) autoantibodies recognize an epitope on the first domain of beta2GPI.
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.
Iverson
G M
GM
La Jolla Pharmaceutical Company, San Diego, CA 92121, USA. mike.iverson@ljpc.com
Victoria
E J
EJ
Marquis
D M
DM
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
D000925:Anticoagulants; D001323:Autoantibodies; D000939:Epitopes; D006023:Glycoproteins; D011994:Recombinant Proteins; D053482:beta 2-Glycoprotein I