title: Immunochemical properties and pathological relevance of anti-β₂-glycoprotein I antibodies of different avidity.
abstract: Despite available treatment, there is still significant morbidity and mortality present among patients with the autoimmune thrombophilic condition termed 'antiphospholipid syndrome' (Espinosa, G. and Cervera, R. 2009. Morbidity and mortality in the antiphospholipid syndrome. Curr. Opin. Pulm. Med. 15:413.). High-avidity (HAv) anti-β(2)-glycoprotein I (anti-β(2)GPI) antibodies, shown to correlate with thrombotic events in patients, could represent the much needed improved prognostic marker. By studying their effect on crystalline annexin A5 shield on phospholipid surfaces (one of proposed pathogenic mechanisms), with the use of atomic force microscopy, the pathogenic potential of HAv anti-β(2)GPI antibodies was confirmed. Furthermore, by using surface plasmon resonance and enzyme-linked immunosorbent assays, unique binding characteristics of HAv antibodies in comparison with low avidity antibodies were established. HAv anti-β(2)GPI were confirmed to (i) recognize β(2)-glycoprotein I in a solution, (ii) interact predominantly monovalently (much lower dependency on the antigen density) and (iii) form more stable complexes with the antigen. Since enzyme-linked immunosorbent assays currently used in routine diagnostics detect anti-β(2)GPI antibodies of unknown avidity, our observations are potentially useful for the development of improved diagnostic tests capable of detecting clinically relevant antibodies.
authors.affiliation: Department of Rheumatology, University Medical Centre Ljubljana, SI-1000 Ljubljana, Slovenia.
authors.forename: Urška
authors.initials: U
authors.lastname: Žager
authors.forename: Špela
authors.initials: Š
authors.lastname: Irman
authors.forename: Mojca
authors.initials: M
authors.lastname: Lunder
authors.forename: Miha
authors.initials: M
authors.lastname: Škarabot
authors.forename: Igor
authors.initials: I
authors.lastname: Muševič
authors.forename: Vesna
authors.initials: V
authors.lastname: Hodnik
authors.forename: Gregor
authors.initials: G
authors.lastname: Anderluh
authors.forename: Saša
authors.initials: S
authors.lastname: Čučnik
authors.forename: Tanja
authors.initials: T
authors.lastname: Kveder
authors.forename: Blaž
authors.initials: B
authors.lastname: Rozman
authors.forename: Borut
authors.initials: B
authors.lastname: Božič
mesh_terms: D017304:Annexin A5 / Q000737:chemistry / Q000378:metabolism; D000906:Antibodies / Q000276:immunology* / Q000378:metabolism; D000915:Antibody Affinity / Q000276:immunology*; D016736:Antiphospholipid Syndrome / Q000276:immunology / Q000378:metabolism; D015374:Biosensing Techniques; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000378:metabolism; D008567:Membranes, Artificial; D018625:Microscopy, Atomic Force; D011485:Protein Binding / Q000276:immunology; D053482:beta 2-Glycoprotein I / Q000037:antagonists & inhibitors / Q000276:immunology*
chemical_list: D017304:Annexin A5; D000906:Antibodies; D008567:Membranes, Artificial; D053482:beta 2-Glycoprotein I