Vitamin D: an instrumental factor in the anti-phospholipid syndrome by inhibition of tissue factor expression
- N Agmon-Levin1,
- M Blank1,
- G Zandman-Goddard2,
- H Orbach3,
- P L Meroni4,
- A Tincani5,
- A Doria6,
- R Cervera7,
- W Miesbach8,
- L Stojanovich9,
- V Barak10,
- B S Porat-Katz11,
- H Amital12,
- Y Shoenfeld13
- 1The Zabludowicz Center for Autoimmune Diseases and Department of Medicine B, Sheba Medical Center, Tel Hashomer, Israel
- 2Department of Medicine ‘C’, Wolfson Medical Centre, Holon, Israel and Sackler Faculty of Medicine Tel Aviv University, Tel Aviv, Israel
- 3Department of Medicine ‘B’, Wolfson Medical Centre, Holon, Israel and Sackler Faculty of Medicine Tel Aviv University, Tel Aviv, Israel
- 4Department of Internal Medicine, University of Milan, IRCCS Istituto Auxologico Italiano, Milan, Italy
- 5Rheumatology and Clinical Immunology, Spedali Civili and University of Brescia, Brescia, Italy
- 6Division of Rheumatology, University of Padova, Padova, Italy
- 7Department of Autoimmune Diseases, Servei de Malalties Autoimmunes, Hospital Clínic, Barcelona, Catalonia, Spain
- 8Medical Clinic III, Institute of Transfusion Medicine, Goethe University, Frankfurt, Germany
- 9“Bezhanijska Kosa”, University Medical Center, Belgrade University, Serbia
- 10Immunology Laboratory for Tumor Diagnosis, Hadassah-Hebrew University Medical Centre, Jerusalem, Israel
- 11Faculty of Agriculture, The Hebrew University Jerusalem, Jerusalem, Israel
- 12Department of Internal Medicine, ‘D’ Meir Medical Centre, Kfar-Saba, Israel and Sackler Faculty of Medicine Tel Aviv University, Tel Aviv, Israel
- 13The Zabludowicz Center for Autoimmune Diseases and Department of Medicine B, Chaim Sheba Medical Center, Tel Hashomer, Israel and Sackler Faculty of Medicine Tel Aviv University, Tel Aviv, Israel
- Correspondence to Dr Yehuda Shoenfeld, The Zabludowicz Center for Autoimmune Diseases, Department of Medicine B, The Chaim Sheba Medical Center, Tel Hashomer 52621, Israel;
- Accepted 20 August 2010
- Published Online First 27 October 2010
Background and aims Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterised by thrombosis, obstetric complications and the presence of anti-phospholipid antibodies such as anti-β2GPI-Abs. These antibodies may set off the coagulation cascade via several mechanisms, including the induction of tissue factor (TF) expression. Vitamin D has recently emerged as an immunomodulator that might exert an anti-thrombotic effect. Therefore, we studied serum vitamin D levels in a cohort of APS patients, as well as the effect of vitamin D in an in vitro model of APS-mediated thrombosis.
Methods Serum vitamin D levels were measured in 179 European APS patients and 141 healthy controls using the LIAISON chemiluminescent immunoassay, and the levels were evaluated in conjunction with a wide spectrum of clinical manifestations. In an vitro model, anti-β2GPI antibodies were purified from four patients with APS to evaluate the expression of TF in activated starved human umbilical vein endothelial cells. The effect of vitamin D (1,25-dihydroxyvitamin D, 10 nm) on anti-β2GPI-Abs mediated TF expression was analysed by immunoblot.
Results Vitamin D deficiency (serum level ≤15 ng/ml) was documented in 49.5% of our APS patients versus 30% of controls (p<0.001) and was significantly correlated with thrombosis (58% vs 42%; p<0.05), neurological and ophthalmic manifestations, pulmonary hypertension, livedo reticularis and skin ulcerations. In vitro vitamin D inhibited the expression of TF induced by anti-β2GPI-antibodies.
Conclusions Vitamin D deficiency is common among APS patients and is associated with clinically defined thrombotic events. Vitamin D inhibits anti-β2GPI-mediated TF expression in vitro. Thus, vitamin D deficiency might be associated with decreased inhibition of TF expression and increased coagulation in APS. Evaluation of vitamin D status and vitamin D supplementation in APS patients should be considered.
Competing interests None.
Patient consent Obtained.
Ethics approval This study was conducted with the approval of the Sheba Medical Center, Israel, and fulfilled the ethical guidelines of the Declaration of Helsinki (Edinburgh, 2000).
Provenance and peer review Not commissioned; externally peer reviewed.