Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Vitamin D: An Instrumental Factor in the Anti-Phospholipids Syndrome Inhibiting Tissue Factor Expression
Agmon-Levin1, Nancy, Glazer1, Maya, Amital2, Howard, Zandman-Goddard3, Gisele, Orbach3, Hedi C., Berliner4, Shlomo, Meroni5, Pierluigi
Center for Autoimmune Diseases, Sheba Medical Center, Ramat Gan, Israel
"Bezhanijska Kosa" University Medical Center, Belgrade, Serbia and Montenegro.
Department of Oncology, Hadassah University Hospital, Jerusalem, Israel
Faculty of Agricultural, The Hebrew University, Jerusalem, Israel
Center for Autoimmune Diseases, Sheba Medical Center, Incumbent of the Laura Schwarz-Kip Chair for Research of Autoimmune Diseases, Tel-Aviv University, Israel
Meir Medical Center, Kfar-Saba, Israel
Wolfson Medical Center, Holon, Israel
Sourasky Medical Center, Tel aviv, Israel
University of Milan, Milan, Italy
University of Brescia, Brescia, Italy
University of Padova, Padova, Italy
Autoimmune Diseases. Hospital Clínic, Barcelona, Spain
Johann Wolfgang Goethe-University, Germany
Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by recurrent thrombotic events and elevated titers of antiphospholipid antibodies (Abs) including anti-beta 2 glycoprotein-I (b2GPI) Abs. Anti-b2GPI-Abs may induce thrombosis via induction of tissue factor (TF) expression, which triggers the coagulation cascade. One of the recently suggested novel roles of Vitamin-D entails immunomodulation and anti-thrombotic mechanisms. Therefore, in a large cohort of APS patients we evaluated vitamin-D levels and its effect in an in vitro model of thrombosis utilizing an anti-b2GPImediated TF expression system.
Patients: Serum concentrations of Vitamin-D were measured in 337 European APS patients with clinically diagnosed thrombotic events (i.e. venous or arterial). We used the Liaison chemiluminescent immunoassay method (DiaSorin-Italy).
We purified anti- b2GPI antibodies from 3 patients with APS and utilized them to activate human endothelial cells (HUVEC) to expresses TF. Vitamin D (1,25-dihydroxyvitamin D, 10nM) was added to starved HUVEC in the presence of anti-b2GPI Abs. TF expression was analyzed by immunoblot utilizing mouse anti-human-TF.
The prevalence of vitamin-D deficiency (<=15ng/ml) was documented in 63% of our APS patients. An increased prevalence of thrombotic events (58%vs. 41%) were documented in patients with vitamin-D deficiency compared to those with higher levels of vitamin-D (P<0.05).
In our experimental model the addition of vitamin-D to endothelial cells significantly inhibited the expression of TF induced by anti-b2GPI Abs purified from the patients.
Vitamin-D deficiency is common among APS patients and associated with clinically diagnosed thrombotic events. Vitamin-D inhibited anti-b2GPI mediated TF expression in an in vitro model. Thus, low levels of Vitamin-D may be associated with decreased inhibition of TF expression and thus increased coagulation in APS.
To cite this abstract, please use the following information:
Agmon-Levin, Nancy, Glazer, Maya, Amital, Howard, Zandman-Goddard, Gisele, Orbach, Hedi C., Berliner, Shlomo, et al; Vitamin D: An Instrumental Factor in the Anti-Phospholipids Syndrome Inhibiting Tissue Factor Expression [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1268