Volume 7 Supplement 1

25th European Workshop for Rheumatology Research

Open Access

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
Arthritis Research & Therapy20057(Suppl 1):P143


Received: 11 January 2005

Published: 17 February 2005


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.

Authors’ Affiliations

Department of Medicine, CME, Karolinska University Hospital
Department of Medicine, Rheumatology Unit and Center for Molecular Medicine, Karolinska University Hospital
Department of Clinical Physiology
Department of Surgery, Karolinska University Hospital


© BioMed Central Ltd 2005