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强直性脊柱炎患者的血管内皮生长因子(VEGF)和骨形态发生蛋白-2(BMP-2)水平及其与肿瘤坏死因子α抑制剂治疗的关系。

The VEGF and BMP-2 levels in patients with ankylosing spondylitis and the relationship to treatment with tumour necrosis factor alpha inhibitors.

作者信息

Tošovský Marian, Bradna Petr, Andrýs Ctirad, Andrýsová Kateřina, Cermáková Eva, Soukup Tomáš

机构信息

Charles University in Prague, Faculty of Medicine in Hradec Králové, and University Hospital Hradec Králové, Czech Republic: 2nd Internal Gastroenterological Department.

Charles University in Prague, Faculty of Medicine in Hradec Králové, and University Hospital Hradec Králové, Czech Republic: Institute of Clinical Immunology and Allergology2.

出版信息

Acta Medica (Hradec Kralove). 2014;57(2):56-61. doi: 10.14712/18059694.2014.40.

Abstract

INTRODUCTION

Ankylosing spondylitis (AS) is an inflammatory rheumatic disease characterized by the development of osteoproductive changes in the spine which could possibly result in ankylosis. Treatment with tumour necrosis factor alpha (TNFα) inhibitors has proved to be an important step forward in the treatment of this disease, but for the time being it is not clear whether it favourably influences radiographic progression of the disease. Vascular endothelial growth factor most probably plays a role in the development of osteoproductive changes and recently its predictive influence on radiographic progression has been demonstrated. Bone morphogenic protein 2 (BMP-2) participates in the regulation of bone proliferation and its increased serum level has been demonstrated in patients with advanced AS and correlated with the degree of radiographic changes.

AIM

The study aims to evaluate the VEGF and BMP-2 levels in patients with ankylosing spondylitis and how these levels relate to the concurrent treatment with TNFα inhibitors.

METHODS

Sera were evaluated from patients at the Rheumatologic Clinic of the Hradec Králové Faculty Hospital who fulfilled the modified New York Criteria for AS (n = 55). In these patients, the parameters of the activity of the disease (BASDAI = Bath Ankylosing Spondylitis Disease Activity Index, CRP = C-reactive protein) and the concurrent therapy (TNFα inhibitors, n = 21, vs. non-anti TNFα, n = 34) were recorded. The levels of VEGF and BMP-2 were analyzed using the ELISA method.

RESULTS

In patients treated with TNFα inhibitors, a significantly lower VEGF level was found when compared to untreated patients (140.3 (109.4; 262.2) vs. 261 (172.4; 396.6) pg/ml; p = 0.02). No difference was found between BMP-2 levels in both groups (treated vs. untreated patients) (254.8 (2301; 267.3) vs. 261.1 (248.6; 273.5) pg/ml; p = 0.24). A correlation analysis did not reveal any relationship between VEG F and BMP-2 (r = 0.057; p = 0.68). Serum levels of VEGF correlated with serum levels of CRP (r = 0.56; p = 0.00001) and the BASDAI value (r = 0.33; p = 0.015).

CONCLUSION

Significantly lower VEGF levels were found in patients treated with TNFα inhibitors versus the untreated patients. These findings are in harmony with some hitherto published analyses and may give evidence of a favourable effect of TNFα inhibitors on radiographic progression. Neither influence on the BMP-2 level by treatment with TNFα inhibitors nor correlation with VEGF levels was demonstrated.

摘要

引言

强直性脊柱炎(AS)是一种炎症性风湿性疾病,其特征是脊柱出现骨质增生性改变,可能导致关节强直。肿瘤坏死因子α(TNFα)抑制剂治疗已被证明是该疾病治疗中的重要进展,但目前尚不清楚它是否对疾病的影像学进展有积极影响。血管内皮生长因子很可能在骨质增生性改变的发展中起作用,最近已证明其对影像学进展有预测影响。骨形态发生蛋白2(BMP - 2)参与骨增殖的调节,在晚期AS患者中已证明其血清水平升高,并与影像学改变程度相关。

目的

本研究旨在评估强直性脊柱炎患者的血管内皮生长因子(VEGF)和骨形态发生蛋白2(BMP - 2)水平,以及这些水平与TNFα抑制剂联合治疗的关系。

方法

对来自赫拉德茨克拉洛韦大学医院风湿病诊所符合改良纽约AS标准的患者(n = 55)的血清进行评估。记录这些患者的疾病活动参数(BASDAI = 巴斯强直性脊柱炎疾病活动指数,CRP = C反应蛋白)和联合治疗情况(TNFα抑制剂,n = 21,与非抗TNFα,n = 34)。采用酶联免疫吸附测定(ELISA)法分析VEGF和BMP - 2水平。

结果

与未治疗患者相比,接受TNFα抑制剂治疗的患者VEGF水平显著降低(140.3(109.4;262.2)对261(172.4;396.6)pg/ml;p = 0.02)。两组(治疗组与未治疗组)的BMP - 2水平无差异(254.8(230.1;267.3)对261.1(248.6;273.5)pg/ml;p = 0.24)。相关性分析未发现VEGF与BMP - 2之间存在任何关系(r = 0.057;p = 0.68)。VEGF血清水平与CRP血清水平(r = 0.56;p = 0.00001)和BASDAI值(r = 0.33;p = 0.015)相关。

结论

接受TNFα抑制剂治疗的患者VEGF水平明显低于未治疗患者。这些发现与一些此前发表的分析结果一致,可能证明TNFα抑制剂对影像学进展有积极作用。未证明TNFα抑制剂治疗对BMP - 2水平有影响,也未证明其与VEGF水平相关。

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