Hanly J G, Smith S A
Division of Rheumatology, Department of Medicine, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada.
Clin Exp Immunol. 2000 Jun;120(3):537-43. doi: 10.1046/j.1365-2249.2000.01248.x.
We examined the role of autoantibodies to beta2-GPI and prothrombin (PT) in the inhibition of annexin V binding to cardiolipin (CL) and the association with clinical manifestations of the anti-phospholipid syndrome (APS). Plasma samples from 59 patients with anti-phospholipid (aPL) antibodies were studied. Affinity purification of total IgG and IgG anti-ss2-GPI antibodies was performed using staphylococcal protein A and phospholipid liposomes. Annexin V binding to CL was significantly inhibited by 31/59 (53%) aPL+ plasma samples. There was a significant association between annexin V inhibition and elevated levels of IgG anti-cardiolipin (aCL) (r = -0.62; P < 0.001), IgG anti-ss2-GPI (r = -0.67; P < 0. 001) and a weaker association with lupus anti-coagulant (r = -0.27; P = 0.05). There was no association with other isotypes of aCL and anti-ss2-GPI or with anti-PT of any isotype. In patients with clinical manifestations of the APS there were higher levels of IgG aCL (median (range) Z score): 10.0 (0-17.6) versus 5.0 (0-16.1); P = 0.03), IgG anti-ss2-GPI (4.5 (0-11.3) versus 0.9 (0-9.7); P = 0.02) and greater inhibition of annexin V binding to CL (-3.4 (-11.4-0.6) versus -1.1 (-10.8-1.2); P = 0.22). Odds ratios for the laboratory assays and the presence of clinical manifestations of the APS varied between 0.38 and 4.16, with the highest values for IgG aCL (4.16), IgG anti-ss2-GPI (3.28) and annexin V inhibition (2.85). Additional experiments with affinity-purified IgG antibodies indicated that inhibition of annexin V binding was dependent upon the concentration of ss2-GPI and anti-ss2-GPI antibodies. These results indicate that inhibition of annexin V binding to procoagulant phospholipid surfaces is dependent upon anti-ss2-GPI antibodies and suggest a role for annexin V in the pathogenesis of the APS.
我们研究了抗β2糖蛋白I（β2-GPI）和凝血酶原（PT）自身抗体在抑制膜联蛋白V与心磷脂（CL）结合中的作用，以及与抗磷脂综合征（APS）临床表现的相关性。对59例抗磷脂（aPL）抗体阳性患者的血浆样本进行了研究。使用葡萄球菌蛋白A和磷脂脂质体对总IgG和抗β2-GPI IgG抗体进行亲和纯化。59份aPL阳性血浆样本中有31份（53%）显著抑制了膜联蛋白V与CL的结合。膜联蛋白V抑制与抗心磷脂（aCL）IgG水平升高（r = -0.62；P < 0.001）、抗β2-GPI IgG水平升高（r = -0.67；P < 0.001）显著相关，与狼疮抗凝物的相关性较弱（r = -0.27；P = 0.05）。与其他aCL和抗β2-GPI同种型或任何同种型的抗PT均无相关性。在有APS临床表现的患者中，aCL IgG水平较高（中位数（范围）Z评分）：10.0（0 - 17.6）对5.0（0 - 16.1）；P = 0.03），抗β2-GPI IgG水平较高（4.5（0 - 11.3）对0.9（0 - 9.7）；P = 0.02），膜联蛋白V与CL结合的抑制作用更强（-3.4（-11.4 - 0.6）对-1.1（-10.8 - 1.2）；P = 0.2）。实验室检测指标与APS临床表现的比值比在0.38至4.16之间，aCL IgG（4.16）、抗β2-GPI IgG（3.28）和膜联蛋白V抑制（2.85）的值最高。用亲和纯化的IgG抗体进行的额外实验表明，膜联蛋白V结合的抑制取决于β2-GPI和抗β2-GPI抗体的浓度。这些结果表明，膜联蛋白V与促凝磷脂表面结合的抑制取决于抗β2-GPI抗体，并提示膜联蛋白V在APS发病机制中起作用。
