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高血压患者抗磷脂抗体的研究

Study of Antiphospholipid Antibodies in Patients with Arterial Hypertension.

作者信息

Romanidou Gioulia, Konstantinidis Theocharis G, Koutsogiannis Odysseas, Grapsa Anastasia, Kantartzi Konstantina, Panagoutsos Stylianos, Panopoulou Maria, Tsigalou Christina

机构信息

Department of Nephrology, Democritus University of Thrace, University General Hospital of Alexandroupolis Dragana Campus, 68100 Alexandroupolis, Greece.

General Hospital "Sismanoglio", Sismanoglou 45, 69133 Komotini, Greece.

出版信息

Med Sci (Basel). 2018 Nov 13;6(4):102. doi: 10.3390/medsci6040102.

Abstract

Antiphospholipid syndrome (APS) is a multifactorial, autoantibody-mediated disease. Antiphospholipid antibodies (aPL) directed against negatively charged phospholipids or various combinations of phospholipid-binding proteins seem to be an independent pathogenic factor that plays a critical role in APS. Unfortunately, their role in hypertension is not fully elucidated. The aim of our study was to determine aPL titers in hypertension patients and investigate the association of aPL with renal impairment parameters. Forty-seven patients with arterial hypertension (22 males, 46.8% and 25 females, 53.2%), aged 41⁻85 years old (mean 65.9 ± 10.1 years), and 21 age-sex-matched subjects without severe hypertension as control group (8 males, 13 females, 38.1% vs. 61.9%), mean age 61 ± 11.3 years, were enrolled in this study. Patients with other risk factors like Rheumatoid Arthritis and Systematic Lupus Erythematosus (SLE), both viral and bacterial acute infections, and cancer were excluded from the study. The aPL (anticardiolipin (ACA) and anti-b2GPI antibodies, IgG and IgM) were measured by ELISA (Aesculisa, Aesku Diagnostics, Wendelsheim, Germany) with a cutoff of 15 GPL/MPL for ACA and 15 U/mL for b2GPI. Serum Neutrophil gelatinase-associated lipocalin (sNGAL) was measured by ELISA kits (BioVendor, Brno, Czech Republic). Biochemical analysis such as serum creatinine (Cr), were measured by automated analyzer and finally estimated glomerular filtration rate (e-GFR) was calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). Fifteen patients were positive for ACA IgG (31.9%), two for anti-b2GPI IgM (4.2%), and three for anti-b2GPI IgG (6.3%). Furthermore, three persons from control group were positive in anti-b2GPI IgG (14.27%). The serum level of anti-b2GPI IgG was significantly higher in patients compared to healthy controls ( = 0.013). The level of sNGAL (59.63 ± 41.5 ng/mL vs. 45.5 ± 21.5 ng/mL, = 0.14) was not higher in hypertensive patients than in the age-sex-matched control group. Additionally, the sNGAL level was found to be directly and positively correlated in patients with positive ACA IgG (r² = 0,945, < 0.0001). These results demonstrate that autoimmunity may be one of the pathogenetic factors of hypertension and aPL antibodies might be a potential marker of renal involvement.

摘要

抗磷脂综合征(APS)是一种多因素、自身抗体介导的疾病。针对带负电荷磷脂或磷脂结合蛋白各种组合的抗磷脂抗体(aPL)似乎是在APS中起关键作用的独立致病因素。遗憾的是,它们在高血压中的作用尚未完全阐明。我们研究的目的是测定高血压患者的aPL滴度,并研究aPL与肾功能损害参数的关联。本研究纳入了47例动脉高血压患者(22例男性,占46.8%;25例女性,占53.2%),年龄在41至85岁之间(平均65.9±10.1岁),以及21例年龄和性别匹配、无严重高血压的受试者作为对照组(8例男性,13例女性,分别占38.1%和61.9%),平均年龄61±11.3岁。患有类风湿关节炎、系统性红斑狼疮(SLE)等其他危险因素、病毒和细菌急性感染以及癌症的患者被排除在研究之外。采用酶联免疫吸附测定法(ELISA,德国温德尔斯海姆的艾斯库诊断公司的Aesculisa)检测aPL(抗心磷脂(ACA)和抗β2糖蛋白I抗体,IgG和IgM),ACA的临界值为15 GPL/MPL,β2糖蛋白I为15 U/mL。采用酶联免疫吸附测定试剂盒(捷克布尔诺的BioVendor公司)检测血清中性粒细胞明胶酶相关脂质运载蛋白(sNGAL)。通过自动分析仪检测血清肌酐(Cr)等生化指标,最后根据慢性肾脏病流行病学协作组(CKD-EPI)公式计算估算肾小球滤过率(e-GFR)。15例患者ACA IgG呈阳性(31.9%),2例抗β2糖蛋白I IgM呈阳性(4.2%),3例抗β2糖蛋白I IgG呈阳性(6.3%)。此外,对照组中有3人抗β2糖蛋白I IgG呈阳性(14.27%)。与健康对照组相比,患者血清抗β2糖蛋白I IgG水平显著更高(P = 0.013)。高血压患者的sNGAL水平(59.63±41.5 ng/mL对45.5±21.5 ng/mL,P = 0.14)并不高于年龄和性别匹配的对照组。此外,发现ACA IgG阳性患者的sNGAL水平呈直接正相关(r² = 0.945,P < 0.0001)。这些结果表明,自身免疫可能是高血压的致病因素之一,aPL抗体可能是肾脏受累的潜在标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ff3/6313595/256f2724ee41/medsci-06-00102-g001.jpg

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