title: Antibodies to age-β2 glycoprotein I in patients with anti-phospholipid antibody syndrome.
abstract: Anti-phospholipid antibody syndrome (APS) is a systemic autoimmune disease characterized clinically by arterial and/or venous thromboses, recurrent abortions or fetal loss and serologically by the presence of 'anti-phospholipid antibodies' (aPL). The main target antigen of the antibodies is β2 glycoprotein I (β2 GPI). Post-translational oxidative modifications of the protein have been widely described. In this study we aimed to analyse sera reactivity to glucose-modified β2 GPI (G-β2 GPI). Sera collected from 43 patients with APS [15 primary APS (PAPS) and 28 APS associated with systemic lupus erythematosus (SLE) (SAPS)], 30 with SLE, 30 with rheumatoid arthritis (RA) and 40 healthy subjects were analysed by an enzyme-linked immunosorbent assay (ELISA) using a G-β2 GPI. Nine of 15 consecutive PAPS out-patients (60%) and 16 of 28 SAPS (57.1%) showed serum antibodies [immunoglobulin (Ig)G class] against G-β2 GPI (anti-G-β2 GPI) by ELISA. The occurrence of anti-G-β2 GPI was significantly higher in APS patients compared to patients suffering from SLE. No RA patients or control healthy subjects resulted positive for anti-G-β2 GPI. Of note, aG-β2 GPI prompted to identify some APS patients (four PAPS and seven SAPS), who were negative in the classical anti-β2 GPI test. Moreover, in APS patients, anti-G-β2 GPI titre was associated significantly with venous thrombosis and seizure in APS patients. This study demonstrates that G-β2 GPI is a target antigen of humoral immune response in patients with APS, suggesting that β2 GPI glycation products may contain additional epitopes for anti-β2 GPI reactivity. Searching for these antibodies may be useful for evaluating the risk of clinical manifestations.
authors.affiliation: Department of Experimental Medicine, 'Sapienza' University of Rome.
authors.forename: M
authors.initials: M
authors.lastname: Sorice
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore Di Sanità
authors.forename: B
authors.initials: B
authors.lastname: Buttari
authors.affiliation: Department of Experimental Medicine, 'Sapienza' University of Rome.
authors.forename: A
authors.initials: A
authors.lastname: Capozzi
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore Di Sanità
authors.forename: E
authors.initials: E
authors.lastname: Profumo
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore Di Sanità
authors.forename: F
authors.initials: F
authors.lastname: Facchiano
authors.affiliation: Department of Internal Medicine and Medical Specialties, 'Sapienza' University of Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Truglia
authors.affiliation: Department of Experimental Medicine, 'Sapienza' University of Rome.
authors.forename: S
authors.initials: S
authors.lastname: Recalchi
authors.affiliation: Department of Internal Medicine and Medical Specialties, 'Sapienza' University of Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Alessandri
authors.affiliation: Department of Internal Medicine and Medical Specialties, 'Sapienza' University of Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Conti
authors.affiliation: Department of Experimental Medicine, 'Sapienza' University of Rome.
authors.forename: R
authors.initials: R
authors.lastname: Misasi
authors.affiliation: Department of Internal Medicine and Medical Specialties, 'Sapienza' University of Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Valesini
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore Di Sanità
authors.forename: R
authors.initials: R
authors.lastname: Riganò
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood / Q000276:immunology; D017153:Antibodies, Anticardiolipin / Q000097:blood / Q000276:immunology; D017152:Antibodies, Antiphospholipid / Q000097:blood / Q000276:immunology; D016736:Antiphospholipid Syndrome / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012640:Seizures / Q000097:blood / Q000276:immunology; D020246:Venous Thrombosis / Q000097:blood / Q000276:immunology; D055815:Young Adult; D053482:beta 2-Glycoprotein I / Q000276:immunology*
chemical_list: D000906:Antibodies; D017153:Antibodies, Anticardiolipin; D017152:Antibodies, Antiphospholipid; D001323:Autoantibodies; D007074:Immunoglobulin G; D053482:beta 2-Glycoprotein I
keywords: anti-phospholipid antibody syndrome; cryptic or neoepitopes; glycation; systemic lupus erythematosus; β2glycoprotein I