title: Annexin A5 anticoagulant activity in children with systemic lupus erythematosus and the association with antibodies to domain I of β2-glycoprotein I.
abstract: Children with systemic lupus erythematosus (SLE) have a high prevalence of antiphospholipid (aPL) antibodies and are at increased risk for aPL-related thrombosis. We investigated the association between annexin A5 anticoagulant activity and antibodies to the domain I portion of β2-glycoprotein I (anti-DI antibodies), and propose a potential mechanism for the pathogenesis of aPL-related thrombosis. Using samples from 183 children with SLE collected during the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial, we examined resistance to the anticoagulant effects of annexin A5, using the annexin A5 resistance (A5R) assay, and evaluated for anti-DI IgG antibodies. Children with SLE had higher frequency of anti-D1 antibodies (p = 0.014) and significantly reduced A5R compared to pediatric controls: mean A5R = 172 ± 30% versus 242 ± 32% (p < 0.0001). Children with SLE and positive anti-DI antibodies had significantly lower mean A5R levels compared to those with negative anti-DI antibodies: mean A5R = 155 ± 24% versus 177 ± 30% (p < 0.0001). In multivariate analysis, anti-DI antibodies (p = 0.013) and lupus anticoagulant (LA) (p = 0.036) were both independently associated with reduced A5R. Children with SLE have significantly reduced annexin A5 anticoagulant activity that is associated with the presence of LA and anti-DI antibodies.
authors.affiliation: Department of Pediatrics, Division of Pediatric Rheumatology, Children's Hospital at Montefiore, Bronx, NY 10467, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Wahezi
authors.forename: N T
authors.initials: NT
authors.lastname: Ilowite
authors.forename: X X
authors.initials: XX
authors.lastname: Wu
authors.forename: L
authors.initials: L
authors.lastname: Pelkmans
authors.forename: B
authors.initials: B
authors.lastname: Laat
authors.forename: L E
authors.initials: LE
authors.lastname: Schanberg
authors.forename: J H
authors.initials: JH
authors.lastname: Rand
mesh_terms: D000293:Adolescent; D017304:Annexin A5 / Q000378:metabolism*; D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016682:Lupus Coagulation Inhibitor / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D015999:Multivariate Analysis; D011446:Prospective Studies; D055815:Young Adult; D053482:beta 2-Glycoprotein I / Q000276:immunology*
chemical_list: D017304:Annexin A5; D017152:Antibodies, Antiphospholipid; D007074:Immunoglobulin G; D016682:Lupus Coagulation Inhibitor; D053482:beta 2-Glycoprotein I
keywords: Antiphospholipid syndrome; annexin A5; pediatric lupus; β2-glycoprotein I