Journal
LUPUS
Volume 22, Issue 7, Pages 702-711Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/0961203313490241
Keywords
Antiphospholipid syndrome; pediatric lupus; annexin A5; beta 2-glycoprotein I
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Funding
- New York Chapter of the Arthritis Foundation
- National Center for Research Resources (NCRR)
- National Center for Advancing Translational Sciences (NCATS), components of the National Institutes of Health (NIH), through CTSA [UL1RR025750, KL2RR025749, TL1RR025748]
- NIH-NIAMS [NO1AR22265]
- Duke Fred and Edna Mandel Center for Hypertension and Atherosclerosis
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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 beta 2-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.
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