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This article is part of the supplement: 25th European Workshop for Rheumatology Research

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Decreased binding of annexin V to endothelial cells: a novel mechanism of atherothrombosis in patients with systemic lupus erythematosus

A Cederholm1, E Svenungsson2, K Jensen-Urstad3, C Trollmo2, A-K Ulfgren2, J Swedenborg4, G-Z Fei2 and J Frostegård1

Author Affiliations

1 Department of Medicine, CME, Karolinska University Hospital, Huddinge, Sweden

2 Department of Medicine, Rheumatology Unit and Center for Molecular Medicine, Karolinska University Hospital, Solna, Sweden

3 Department of Clinical Physiology, Södersjukhuset, Sweden

4 Department of Surgery, Karolinska University Hospital, Huddinge, Sweden

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Arthritis Research & Therapy 2005, 7(Suppl 1):P143  doi:10.1186/ar1664

The electronic version of this article is the complete one and can be found online at:

Received:11 January 2005
Published:17 February 2005

© 2005 BioMed Central Ltd


Patients with systemic lupus erythematosus (SLE) are at high risk of cardiovascular disease, due to atherothrombosis in particular. The mechanisms are not clear; however, recently annexin V, an anticoagulant protein, and antiphospholipid antibodies have been implicated.


Twenty-six women (52 ± 8.2 years) with SLE and a history of cardiovascular disease (SLE cases) were compared with two age-matched control groups: 26 women with SLE but no cardiovascular disease (SLE controls) and 26 healthy women (population controls). Common carotid intima-media thickness was determined by B-mode ultrasound as a surrogate measure of atherosclerosis. Annexin V binding to human umbilical vein endothelial cells was assessed by flow cytometry after 24-hour culture with plasma. The presence of annexin V in carotid atherosclerotic plaques was determined by immunohistochemistry. Annexin V levels in circulation and anti-annexin IgG and IgM antibodies were measured by a commercially available high-sensitivity ELISA. Pooled sera with high capacity to inhibit annexin V binding were preabsorbed against different concentrations of antigens such as cardiolipin and phosphorylcholine and against unrelated antigen tetanus toxoid. Annexin V-binding assay with flow cytometry was performed.


Binding of annexin V was significantly lower when plasma from SLE cases was used as compared with controls (SLE cases versus population controls P = 0.002, SLE cases versus SLE controls P = 0.02). There was a striking positive association between annexin V binding and intima-media thickness (R = 0.73, P < 0.001) among SLE cases. The annexin V levels were increased in SLE cases compared with both SLE controls and PC (P = 0.03 and P = 0.004), but no differences were detected in anti-annexin V IgG or IgM levels. Depletion of IgG from sera with high capacity to inhibit binding of annexin V induced a 2.7-fold increase in binding and preincubation of sera with cardiolipin and phosphorylcholine resulted in increase of median fluorescence intensity of annexin V binding to human umbilical vein endothelial cells. Immunohistochemical analysis revealed the presence of annexin V in all plaques tested.


Decreased annexin V binding to endothelium caused by immunoglobulin may represent a novel mechanism of atherothrombosis. Increasing annexin V binding may thus represent a novel therapeutic possibility.