title: Pregnancy loss in the antiphospholipid-antibody syndrome--a possible thrombogenic mechanism.
abstract: BACKGROUND
  The mechanisms of vascular thrombosis and pregnancy loss in the antiphospholipid-antibody syndrome are unknown. Levels of annexin V, a phospholipid-binding protein with potent anticoagulant activity, are markedly reduced on placental villi from women with this syndrome. Hypercoagulability in such women may therefore be due to the reduction of surface-bound annexin V by antiphospholipid antibodies. To test this idea, we studied how antiphospholipid antibodies affect levels of annexin V on cultured trophoblasts and human umbilical-vein endothelial cells and how they affect the procoagulant activity of these cells.
  
  
  METHODS
  We isolated IgG fractions from three patients with the antiphospholipid-antibody syndrome and from normal controls. These antibodies were incubated with cultured BeWo cells (a placental-trophoblast cell line), primary cultured trophoblasts, and human umbilical-vein endothelial cells. Annexin V on the cell surfaces was measured by an enzyme-linked immunosorbent assay. The coagulation times of plasma overlaid on the cells were also determined.
  
  
  RESULTS
  Trophoblasts and endothelial cells exposed to antiphospholipid-antibody IgG as compared with control IgG had reduced levels of annexin V (trophoblasts, 0.37 +/- 0.02 vs. 0.85 +/- 0.12 ng per well, P=0.02; endothelial cells, 1.6 +/- 0.04 vs. 2.1 +/- 0.05 ng per well, P=0.001). Also, trophoblasts and endothelial cells exposed to antiphospholipid-antibody IgG had faster mean (+/- SE) plasma coagulation times than cells exposed to control IgG (trophoblasts, 8.7 +/- 2.0 vs. 21.3 +/- 2.9 minutes, P=0.02; endothelial cells, 9.8 +/- 0.8 vs. 14.2 +/- 1.2 minutes, P=0.04).
  
  
  CONCLUSIONS
  Antiphospholipid antibodies reduce the levels of annexin V and accelerate the coagulation of plasma on cultured trophoblasts and endothelial cells. The reduction of annexin V levels on vascular cells may be an important mechanism of thrombosis and pregnancy loss in the antiphospholipid-antibody syndrome.
authors.affiliation: Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Rand
authors.forename: X X
authors.initials: XX
authors.lastname: Wu
authors.forename: H A
authors.initials: HA
authors.lastname: Andree
authors.forename: C J
authors.initials: CJ
authors.lastname: Lockwood
authors.forename: S
authors.initials: S
authors.lastname: Guller
authors.forename: J
authors.initials: J
authors.lastname: Scher
authors.forename: P C
authors.initials: PC
authors.lastname: Harpel
mesh_terms: D000022:Abortion, Spontaneous / Q000209:etiology / Q000276:immunology* / Q000503:physiopathology; D017304:Annexin A5 / Q000032:analysis* / Q000276:immunology; D017152:Antibodies, Antiphospholipid / Q000276:immunology / Q000502:physiology*; D016736:Antiphospholipid Syndrome / Q000150:complications / Q000276:immunology* / Q000503:physiopathology; D001777:Blood Coagulation / Q000276:immunology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000737:chemistry; D005260:Female; D006801:Humans; D007074:Immunoglobulin G; D011247:Pregnancy / Q000276:immunology / Q000502:physiology; D012016:Reference Values; D014327:Trophoblasts / Q000737:chemistry*; D014471:Umbilical Veins / Q000737:chemistry*
chemical_list: D017304:Annexin A5; D017152:Antibodies, Antiphospholipid; D007074:Immunoglobulin G