title: Vitamin D: an instrumental factor in the anti-phospholipid syndrome by inhibition of tissue factor expression.
abstract: OBJECTIVE
  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.
authors.affiliation: The Zabludowicz Center for Autoimmune Diseases and Department of Medicine B, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: N
authors.initials: N
authors.lastname: Agmon-Levin
authors.forename: M
authors.initials: M
authors.lastname: Blank
authors.forename: G
authors.initials: G
authors.lastname: Zandman-Goddard
authors.forename: H
authors.initials: H
authors.lastname: Orbach
authors.forename: P L
authors.initials: PL
authors.lastname: Meroni
authors.forename: A
authors.initials: A
authors.lastname: Tincani
authors.forename: A
authors.initials: A
authors.lastname: Doria
authors.forename: R
authors.initials: R
authors.lastname: Cervera
authors.forename: W
authors.initials: W
authors.lastname: Miesbach
authors.forename: L
authors.initials: L
authors.lastname: Stojanovich
authors.forename: V
authors.initials: V
authors.lastname: Barak
authors.forename: B S
authors.initials: BS
authors.lastname: Porat-Katz
authors.forename: H
authors.initials: H
authors.lastname: Amital
authors.forename: Y
authors.initials: Y
authors.lastname: Shoenfeld
mesh_terms: D000328:Adult; D016736:Antiphospholipid Syndrome / Q000097:blood* / Q000150:complications; D016022:Case-Control Studies; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013925:Thromboplastin / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D013927:Thrombosis / Q000209:etiology; D014807:Vitamin D / Q000097:blood* / Q000494:pharmacology; D014808:Vitamin D Deficiency / Q000097:blood / Q000150:complications*; D014815:Vitamins / Q000494:pharmacology; D053482:beta 2-Glycoprotein I / Q000276:immunology
chemical_list: D014815:Vitamins; D053482:beta 2-Glycoprotein I; D014807:Vitamin D; D013925:Thromboplastin