title: IgG antibodies that recognize epitope Gly40-Arg43 in domain I of beta 2-glycoprotein I cause LAC, and their presence correlates strongly with thrombosis.
abstract: Anti-beta(2)-glycoprotein I antibodies are known to have a heterogeneous reactivity against beta(2)-glycoprotein I. We performed this study to characterize the epitope on beta(2)-glycoprotein I to which pathologic anti-beta(2)-glycoprotein I antibodies are directed. Plasma samples from 198 patients with various systemic autoimmune diseases were tested for the presence of lupus anticoagulant and anti-beta(2)-glycoprotein I immunoglobulin G (IgG) antibodies. The reactivity of the anti-beta(2)-glycoprotein I-positive samples was further tested by coating recombinant full-length beta(2)-glycoprotein I and 8 deletion mutants of beta(2)-glycoprotein I onto hydrophilic and hydrophobic enzyme-linked immunosorbent assay (ELISA) plates. Full-length beta(2)-glycoprotein I with point mutations in domain I at positions 8, 40, and 43 were used in inhibition experiments. Fifty-two patients with anti-beta(2)-glycoprotein I IgG antibodies could be divided into 2 patterns. Type A antibodies only recognize domain I when coated onto hydrophobic plates; they do not recognize domain I coated onto hydrophilic plates. Type B antibodies have heterogeneous reactivity for all domains. Type A antibodies recognize the epitope around amino acids Gly40-Arg43 and cause lupus anticoagulant activity. In contrast to type B antibodies, those of type A strongly correlated with thrombosis. In conclusion, antibodies directed at domain I (epitope comprising Gly40 and Arg43) have lupus anticoagulant activity and strongly associate with thrombosis.
authors.affiliation: Department of Haematology, University Medical Centre Utrecht, PO Box 85500, 3584CX Utrecht, the Netherlands.
authors.forename: Bas
authors.initials: B
authors.lastname: de Laat
authors.forename: Ronald H W M
authors.initials: RH
authors.lastname: Derksen
authors.forename: Rolf T
authors.initials: RT
authors.lastname: Urbanus
authors.forename: Philip G
authors.initials: PG
authors.lastname: de Groot
mesh_terms: D000328:Adult; D000918:Antibody Specificity; D001120:Arginine; D001666:Binding Sites, Antibody; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005998:Glycine; D006023:Glycoproteins / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000378:metabolism*; D016682:Lupus Coagulation Inhibitor / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D008297:Male; D016017:Odds Ratio; D017434:Protein Structure, Tertiary; D013927:Thrombosis / Q000097:blood / Q000276:immunology*; D053482:beta 2-Glycoprotein I
chemical_list: D000939:Epitopes; D006023:Glycoproteins; D007074:Immunoglobulin G; D016682:Lupus Coagulation Inhibitor; D053482:beta 2-Glycoprotein I; D001120:Arginine; D005998:Glycine