系统性红斑狼疮患者中β2糖蛋白I、凝血酶原、蛋白C、蛋白S和膜联蛋白V抗体的流行率与血栓形成及血小板减少并发症之间的关联

Association between the prevalence of antibodies to beta(2)-glycoprotein I, prothrombin, protein C, protein S, and annexin V in patients with systemic lupus erythematosus and thrombotic and thrombocytopenic complications.

作者信息

Nojima J, Kuratsune H, Suehisa E, Futsukaichi Y, Yamanishi H, Machii T, Iwatani Y, Kanakura Y

机构信息

Central Laboratory for Clinical Investigation, Osaka University Hospital, 2-15 Yamadaoka, Suita, Osaka 565-0871, Japan.

出版信息

Clin Chem. 2001 Jun;47(6):1008-15.

PMID:11375285

Abstract

BACKGROUND

Anti-phospholipid (aPL) antibodies (Abs) frequently found in the plasma of patients with systemic lupus erythematosus (SLE) have been associated with thrombotic complications. Our aim was to clarify the roles in thrombosis of aPL Abs that react with complexes of phospholipids and plasma proteins such as beta(2)-glycoprotein I (beta(2)-GPI), prothrombin, protein C, protein S, and annexin V.

METHODS

We determined the prevalence of aPL Abs to various phospholipid-binding plasma proteins in SLE patients with arterial thrombosis (30 cases), venous thrombosis (19 cases), thrombocytopenia (14 cases), fetal loss (14 cases), and patients without complications (91 cases). The aPL Abs were measured by an ELISA system in which human plasma proteins (beta(2)-GPI, prothrombin, protein C, protein S, and annexin V) were immobilized on gamma-irradiated or plain polystyrene plates.

RESULTS

All types of aPL Abs were frequently observed in the patients with SLE when gamma-irradiated polystyrene plates were used (51 of 168 cases positive for anti-beta(2)-GPI, 94 of 168 cases positive for anti-prothrombin, 36 of 168 cases positive for anti-protein C, 47 of 168 cases positive for anti-protein S, and 50 of 168 cases positive for anti-annexin V), whereas no Abs to these plasma proteins were detected when plain polystyrene plates were used. Multivariate analysis confirmed that both anti-beta(2)-GPI and anti-prothrombin Abs were significant risk factors for arterial thrombosis [odds ratios (ORs), 8.8 and 14.5, respectively; 95% confidence intervals (CIs), 3.2-25 and 1.8-116, respectively] but not for venous thrombosis. The presence of anti-protein S Abs was a significant risk factor for venous thrombosis (OR, 30.4; CI, 3.3-281) but not for arterial thrombosis. The only significant risk factor for fetal loss was the presence of anti-annexin V Abs (OR, 5.9; CI, 1.4-14.8).

CONCLUSIONS

Patients with SLE frequently have some aPL Abs to beta(2)-GPI, prothrombin, protein C, protein S, and annexin V. Thrombotic complications in SLE may depend on the antigenic specificities of these Abs, alone or in combination.

摘要

背景

系统性红斑狼疮（SLE）患者血浆中常见的抗磷脂（aPL）抗体与血栓形成并发症有关。我们的目的是阐明与磷脂和血浆蛋白复合物（如β2-糖蛋白I（β2-GPI）、凝血酶原、蛋白C、蛋白S和膜联蛋白V）反应的aPL抗体在血栓形成中的作用。

方法

我们测定了动脉血栓形成的SLE患者（30例）、静脉血栓形成的SLE患者（19例）、血小板减少症患者（14例）、胎儿丢失患者（14例）以及无并发症患者（91例）中针对各种磷脂结合血浆蛋白的aPL抗体的患病率。通过酶联免疫吸附测定（ELISA）系统检测aPL抗体，该系统将人血浆蛋白（β2-GPI、凝血酶原、蛋白C、蛋白S和膜联蛋白V）固定在经γ射线照射的或普通的聚苯乙烯板上。

结果

当使用经γ射线照射的聚苯乙烯板时，SLE患者中经常观察到所有类型的aPL抗体（168例中有51例抗β2-GPI阳性，168例中有94例抗凝血酶原阳性，168例中有36例抗蛋白C阳性，168例中有47例抗蛋白S阳性，168例中有50例抗膜联蛋白V阳性），而当使用普通聚苯乙烯板时，未检测到针对这些血浆蛋白的抗体。多变量分析证实，抗β2-GPI和抗凝血酶原抗体都是动脉血栓形成的显著危险因素[优势比（OR）分别为8.8和14.5；95%置信区间（CI）分别为3.2 - 25和1.8 - 116]，但不是静脉血栓形成的危险因素。抗蛋白S抗体的存在是静脉血栓形成的显著危险因素（OR，30.4；CI，3.3 - 281），但不是动脉血栓形成的危险因素。胎儿丢失的唯一显著危险因素是抗膜联蛋白V抗体的存在（OR，5.9；CI，1.4 - 14.8）。