Pregnancy loss in the antiphospholipid-antibody syndrome - A possible thrombogenic mechanism
Pregnancy loss in the antiphospholipid-antibody syndrome - A possible thrombogenic mechanism
复制标题
DOI：
10.1056/nejm199707173370303
复制
发表时间：
1997-07-17
影响因子：
158.5
通讯作者：
Harpel, PC
中科院分区：
文献类型：
--
作者：
Rand, JH;Wu, XX;Harpel, PC
背景抗磷脂抗体综合征血管血栓形成和妊娠丧失的机制尚不清楚。膜联蛋白V（一种具有有效抗凝活性的磷脂结合蛋白）的水平在患有这种综合征的妇女胎盘绒毛上显著降低。因此，这些妇女的高凝性可能是由于抗磷脂抗体减少了表面结合的膜联蛋白V。为了验证这一观点，我们研究了抗磷脂抗体如何影响培养的滋养细胞和人脐静脉内皮细胞的膜联蛋白V水平，以及它们如何影响这些细胞的促凝活性。方法从3例抗磷脂抗体综合征患者和正常对照中分离IgG。这些抗体与培养的BeWo细胞（一种胎盘滋养细胞系）、原代培养的滋养细胞和人脐静脉内皮细胞一起孵育。用酶联免疫吸附法测定细胞表面的膜联蛋白V。同时测定覆盖在细胞上的血浆凝固时间。结果与对照组IgG相比，暴露于抗磷脂抗体IgG的滋养细胞和内皮细胞膜联蛋白V水平降低（滋养细胞，0.37+/-0.02 vs. 0.85+/-0.12 ng /孔，P=0.02；内皮细胞，1.6+/-0.04 vs. 2.1+/-0.05 ng /孔，P=0.001）。此外，暴露于抗磷脂抗体IgG的滋养细胞和内皮细胞的平均（+/-SE）血浆凝固时间比暴露于对照IgG的细胞更快（滋养细胞，8.7+/-2.0 vs. 21.3+/-2.9分钟，P=0.02；内皮细胞，9.8+/-0.8 vs. 14.2+/-1.2分钟，P=0.04）。结论抗磷脂抗体可降低培养的滋养细胞和内皮细胞膜联蛋白V水平，加速血浆凝固。血管细胞膜联蛋白V水平的降低可能是抗磷脂抗体综合征患者血栓形成和妊娠丧失的重要机制。(C)1997年，马萨诸塞州医学协会。
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. (C)1997, Massachusetts Medical Society.