北京大学学报(医学版) ›› 2018, Vol. 50 ›› Issue (6): 1027-1032. doi: 10.19723/j.issn.1671-167X.2018.06.015

• 论著 • 上一篇    下一篇

可溶性内皮糖蛋白在抗磷脂综合征患者的血清水平及临床意义

李记1,2,郑莉1,石连杰2,徐婧2,舒建龙3,张学武3,()   

  1. 1. 北京大学人民医院风湿免疫科, 北京 100044
    2. 北京大学国际医院风湿免疫科, 北京 102206
    3. 广西国际壮医医院风湿病科, 南宁 530011
  • 收稿日期:2018-07-10 出版日期:2018-12-18 发布日期:2018-12-18
  • 通讯作者: 张学武 E-mail:xuewulore@163.com

Increased serum soluble-endoglin level and its clinical significance in antiphospholipid syndrome

Ji LI1,2,Li ZHENG1,Lian-jie SHI2,Jing XU2,Jian-long SHU3,Xue-wu ZHANG3,()   

  1. 1. Department of Rheumatology and Immunology, Peking University People’ s Hospital, Beijing 100044, China
    2. Department of Rheumatology and Immunology, Peking University International Hospital, Beijing 102206, China
    3. Department of Rheumatology and Immunology, Guangxi International Zhuang Medical Hospital, Nanning 530011, China
  • Received:2018-07-10 Online:2018-12-18 Published:2018-12-18
  • Contact: Xue-wu ZHANG E-mail:xuewulore@163.com

摘要:

目的: 检测可溶性内皮糖蛋白(soluble endoglin,s-Eng)在抗磷脂综合征(antiphospholipid syndrome,APS)患者的血清水平并分析其潜在临床意义。方法: 采用酶联免疫吸附试验方法检测139例APS患者[原发性APS患者64例,继发于系统性红斑狼疮(systemic lupus erythematosus,SLE)的APS患者75例]、44例不符合APS诊断的单纯SLE患者、37例原发性干燥综合征(primary sjogren syndrome,pSS)患者、23例白塞病(Behcet’s disease,BD)患者、22例系统性硬化病(systemic sclerosis,SSc)患者、22例持续抗心磷脂抗体(anticardiolipin antibody,aCL)阳性但无法诊断SLE或APS者(单纯aCL阳性组)及87例健康对照(health control,HC)的s-Eng血清水平,分析APS患者外周血s-Eng水平与其临床及实验室表现的关系。数据分析采用 t检验、方差分析、Mann-Whitney U 检验、Pearson’s χ 2检验。 结果: (1)APS患者血清s-Eng水平[(10.15±4.64) mg/L]显著高于其他风湿病患者[单纯SLE(5.55±2.51) mg/L,pSS(5.32±2.34) mg/L,BD(4.58±1.53) mg/L, SSc(7.11±4.18) mg/L]、单纯aCL阳性组[(5.17±2.00) mg/L]及HC组[(5.04±1.11) mg/L],P均小于0.001。原发性APS患者与继发于SLE的APS患者血清s-Eng水平差异无统计学意义[(9.83±5.15) mg/L vs. (10.42±4.18) mg/L,P =0.12]。单纯aCL阳性组血清s-Eng水平与HC组差异无统计学意义[(5.17±2.00) mg/L vs.(5.04±1.11) mg/L, P>0.05]。(2)以正常对照者血清s-Eng的 x - ±3s作为诊断APS的cut-off值,将APS患者血清s-Eng≥8.37 mg/L设为s-Eng阳性组,对应的敏感性为0.772,特异性为0.928;约登指数为0.700。(3)s-Eng阳性组患者出现动脉血栓事件、病态妊娠比例显著高于s-Eng阴性组患者[分别为46/81 vs. 19/58, P<0.05; 29/65 vs. 10/44, P<0.05];s-Eng阳性组患者的血小板水平显著低于s-Eng阴性组患者(72.00×10 9/L vs. 119.00×10 9/L, P<0.001)。(4)s-Eng阳性组患者抗心磷脂抗体(anticardiolipin antibody,aCL)阳性的比例(93.83% vs. 37.93%, P<0.001)及抗体滴度(61.70 U/mL vs. 15.45 U/mL,P<0.001)均高于s-Eng阴性组。抗β2-糖蛋白Ⅰ抗体阳性的比例(61.73% vs. 43.10%, P<0.05)及抗体滴度(33.48 U/mL vs. 17.40 U/mL,P<0.05)也均高于s-Eng阴性组。 结论: s-Eng在APS患者血清中异常升高,其有可能为APS的诊断及风险预测提供一个血清学标志的补充。

关键词: 可溶性内皮糖蛋白, 抗磷脂综合征, 血栓形成, 病态妊娠, 抗磷脂抗体

Abstract:

Objective: To detect the serum levels of soluble endothelial glycoprotein endoglin (s-Eng) in patients with antiphospholipid syndrome(APS) and to evaluate the correlation between s-Eng levels and clinical features and laboratory parameters.Methods:The levels of serum s-Eng were measured by enzyme linked immunosorbent assay ( ELISA) in 139 patients with APS, 44 patients with SLE but no APS, 37 patients with primary Sjogren’s syndrome (pSS), 23 patients with Bechet’s disease (BD), 22 patients with systemic sclerosis (SSc) and 22 persistent anticardiolipin antibody (aCL) positive indivi-duals without SLE or APS(simply aCL positive group) and 87 health controls(HC) without any auto-immune diseases. These APS patients included 64 primary APS patients and 75 APS patients secondary to SLE.The correlation between the clinical data, laboratory parameters, and serum s-Eng levels were analyzed.Independent samples t test,paired t test,Chi-square Test, Mann-Whitney U test, Pearson’s χ 2 test were used for statistical analyses. Results:(1)The serum levels of s-Eng were significantly higher in the patients with APS whether primary or secondary to SLE than in the health controls and simply aCL positive group and the patients with other autoimmune diseases, including SLE, pSS, BD and SSc(P<0.001).There was no significant difference in the serum s-Eng levels between simply aCL positive group and health controls[(5.17±2.00) mg/L vs.(5.04±1.11) mg/L, P>0.05]. (2) The best cut-off value for the diagnosis of APS was no less than 8.37 mg/L as mean ± 3SD value, with the sensitivity at 0.772 and the specificity at 0.928. The Youden index was 0.700. These results indicated good validity of s-Eng as a diagnostic marker for APS. (3)The proportions of artery thrombosis and pathological pregnancy were higher in the group of s-Eng -positive APS patients than that in s-Eng -negative group(46/81 vs. 19/58,29/65 vs. 10/44,respectively, all P<0.05).The levels of PLT were lower in the group of s-Eng-positive APS patients (72.00×10 9/L vs. 119.00×10 9/L, P<0.001). (4)The proportions of the presence(93.83% vs. 37.93%, P<0.001) and titer (61.70 U/mL vs.15.45 U/mL, P<0.001) of aCL were both higher in the group of s-Eng-positive APS patients than in s-Eng-negative group. The proportions of the presence (61.73% vs. 43.10%, P<0.05)and titer (33.48 U/mL vs.17.40 U/mL,P<0.05) of anti-β2-glycoproteinⅠ antibody were both higher in the group of s-Eng -positive APS patients than in s-Eng -negative group too. Conclusion:S-Eng serum levels were significantly increased in the patients with APS, and it may play a role as acomplementary serological marker for the diagnosis and risk prediction of APS.

Key words: Soluble endoglin, Antiphospholipid syndrome, Thrombosis, Pathological pregnancy, Antiphospholipid antibody

中图分类号: 

  • R593.2

表1

抗磷脂综合征患者一般资料及临床实验室特征"

Parameter APS patients (n=139)
Demographic data
Age/years, x-±s 43.05±15.33
Disease duration/years, x-±s 4.35±2.92
Male / female 30/109
Clinical manifestation
Tarombokinesis 137/139 (98.56%)
Arterial thrombosis 65/139 (46.76%)
Venous thrombosis 96/139 (58.27%)
Microvascular thrombosis 15/139 (10.79%)
Obstetrical complications 39/109 (35.78%)
Dead fetus in uterus 22/109 (20.18%)
Spontaneous abortion ≥3 times 14/109 (9.17%)
Preeclampsia 3/109 (2.75%)
Laboratory characteristics
Hematological disease 67/139 (48.25%)
Thrombocytopenia 85/139 (61.2%)
Anemia 39/139 (60.43%)
ANA 84/139 (60.43%)
LA 15/24 (62.5%)
aCL 98/139 (70.50%)
Antiβ2-GPⅠ 75/139 (53.96%)

图1

抗磷脂综合征患者、其他风湿病患者、单纯抗心磷脂抗体 阳性者及健康对照的血清可溶性内皮糖蛋白水平"

图2

原发性抗磷脂综合征与系统性红斑狼疮继发抗磷脂综合征患者血清可溶性内皮糖蛋白水平"

图3

可溶性内皮糖蛋白用于诊断抗磷脂综合征的ROC曲线"

表2

抗磷脂综合征患者中可溶性内皮糖蛋白阳性组与可溶性内皮糖蛋白阴性组临床及实验室检查特征的比较"

Parameter s-Eng(+) s-Eng(-) P
Demographic data
Age/years, x-±s 43.05±15.32 41.10±15.00 0.491
Disease duration /years, x-±s 4.42±3.17 4.20±2.22 0.686
Male/female 16/65 14/44 0.535
Clinical feature
Tarombokinesis 80/81 57/58 1.000
Arterial thrombosis 46/81 19/58 0.005
Venous thrombosis 59/81 37/58 0.255
Microvascular thrombosis 11/81 4/58 0.210
Obstetrical complications 29/65 10/44 0.019
Dead fetus in uterus 15/65 7/44 0.360
Spontaneous abortion ≥3 times 12/65 2/44 0.033
Preeclampsia 2/65 1/44 0.799
Laboratory examination
Hematological disease 63/81 26/58 <0.001
WBC(×109/L), x-±s 6.11±3.45 5.87±3.87 0.720
PLT(×109/L), M(P25,P75) 72.00 (52.00, 99.70) 119.00 (89.75, 162.70) <0.001
HGB/(g/L), x-±s 120.63±28.89 128.23±26.09 0.147
LA (+) 18/81 11/58 0.928
aCL (+) 76/81 22/58 <0.001
Antiβ2-GPⅠ (+) 50/81 25/58 0.030
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