The vascular endothelial growth factor as a candidate biomarker of systemic lupus erythematosus: a GRADE-assessed systematic review and meta-analysis

IF 3.2 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Clinical and Experimental Medicine Pub Date : 2024-09-11 DOI:10.1007/s10238-024-01487-w
Arduino A. Mangoni, Angelo Zinellu
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Abstract

There is an ongoing search for novel biomarkers of endothelial damage, active disease, and organ dysfunction in systemic lupus erythematosus (SLE). We investigated the role of the vascular endothelial growth factor (VEGF) as a candidate biomarker by conducting a systematic review and meta-analysis of studies examining VEGF concentrations in SLE patients and healthy controls. We searched electronic databases (PubMed, Scopus, and Web of Science) from inception to 31 May 2024 (inclusion criteria: VEGF measurement in SLE patients and healthy controls and SLE patients with and without active disease or specific organ dysfunction in case–control studies, recruitment of adult participants, and availability of the full text in the English language; exclusion criteria: non-case–control studies, participants under 18 years, articles reporting duplicate or irrelevant data, and animal studies). We assessed the risk of bias and the certainty of evidence using the JBI Critical Appraisal Checklist and GRADE, respectively (PROSPERO registration number: CRD42024561636). Circulating VEGF concentrations were significantly higher in SLE patients than in controls (22 studies; standardised mean difference, SMD = 0.71, 95% CI 0.44 to 0.98, p < 0.001; low certainty of evidence). In SLE patients, VEGF concentrations were significantly higher in those with active disease (six studies; SMD = 1.10, 95% CI 0.27 to 1.92, p = 0.009; very low certainty of evidence) and lupus nephritis (four studies; SMD = 0.80, 95% CI 0.03 to 1.57, p = 0.042; very low certainty of evidence). Only one study reported VEGF concentrations in SLE patients with and without pulmonary arterial hypertension. The effect size of the differences in VEGF concentrations between SLE patients and controls was not associated with disease duration, use of glucocorticoids and immunosuppressors, biological matrix assessed, or analytical method used. However, it was significantly associated with the study’s geographical location. The evidence was limited by the high but partially explainable heterogeneity and the presence of publication bias which was addressed with the “trim-and-fill” method (SLE presence), the high but partially explainable heterogeneity and lack of assessment of publication bias because of the limited study number (active disease), and the limited study number preventing the identification of sources of heterogeneity, sensitivity analysis, and assessment of publication bias (lupus nephritis). Our results highlight VEGF’s potential role as a SLE biomarker and the need for further research, also given the aforementioned limitations, investigating VEGF concentrations in a wide range of SLE patient subgroups.

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作为系统性红斑狼疮候选生物标志物的血管内皮生长因子:GRADE 评估系统综述和荟萃分析
人们一直在寻找系统性红斑狼疮(SLE)内皮损伤、活动性疾病和器官功能障碍的新型生物标志物。我们通过对系统性红斑狼疮患者和健康对照组中血管内皮生长因子浓度的研究进行系统回顾和荟萃分析,探讨了血管内皮生长因子(VEGF)作为候选生物标志物的作用。我们检索了从开始到 2024 年 5 月 31 日的电子数据库(PubMed、Scopus 和 Web of Science)(纳入标准:系统性红斑狼疮患者的血管内皮生长因子测量):病例对照研究中系统性红斑狼疮患者和健康对照者以及伴有或不伴有活动性疾病或特定器官功能障碍的系统性红斑狼疮患者的血管内皮生长因子测量结果,招募成年参与者,并提供英文全文;排除标准:非病例对照研究、18 岁以下参与者、报告重复或不相关数据的文章以及动物研究)。我们分别使用 JBI 临界评估清单和 GRADE 评估了偏倚风险和证据的确定性(PROSPERO 注册号:CRD42024561636)。系统性红斑狼疮患者的循环血管内皮生长因子浓度明显高于对照组(22 项研究;标准化平均差,SMD = 0.71,95% CI 0.44 至 0.98,p < 0.001;证据确定性低)。在系统性红斑狼疮患者中,活动性疾病(6 项研究;SMD = 1.10,95% CI 0.27 至 1.92,p = 0.009;证据确定性极低)和狼疮肾炎(4 项研究;SMD = 0.80,95% CI 0.03 至 1.57,p = 0.042;证据确定性极低)患者的血管内皮生长因子浓度明显更高。只有一项研究报告了伴有和不伴有肺动脉高压的系统性红斑狼疮患者体内的血管内皮生长因子浓度。系统性红斑狼疮患者与对照组之间血管内皮生长因子浓度差异的效应大小与病程、糖皮质激素和免疫抑制剂的使用、评估的生物基质或使用的分析方法无关。不过,这与研究的地理位置有很大关系。证据的局限性在于:异质性较高,但可部分解释;存在发表偏倚,但已通过 "修剪-填充 "方法解决(系统性红斑狼疮);异质性较高,但可部分解释;由于研究数量有限,缺乏对发表偏倚的评估(活动性疾病);研究数量有限,无法识别异质性来源、进行敏感性分析和评估发表偏倚(狼疮肾炎)。我们的研究结果凸显了血管内皮生长因子作为系统性红斑狼疮生物标志物的潜在作用,以及进一步开展研究的必要性,同时也考虑到上述局限性,需要调查各种系统性红斑狼疮患者亚群中血管内皮生长因子的浓度。
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来源期刊
Clinical and Experimental Medicine
Clinical and Experimental Medicine 医学-医学:研究与实验
CiteScore
4.80
自引率
2.20%
发文量
159
审稿时长
2.5 months
期刊介绍: Clinical and Experimental Medicine (CEM) is a multidisciplinary journal that aims to be a forum of scientific excellence and information exchange in relation to the basic and clinical features of the following fields: hematology, onco-hematology, oncology, virology, immunology, and rheumatology. The journal publishes reviews and editorials, experimental and preclinical studies, translational research, prospectively designed clinical trials, and epidemiological studies. Papers containing new clinical or experimental data that are likely to contribute to changes in clinical practice or the way in which a disease is thought about will be given priority due to their immediate importance. Case reports will be accepted on an exceptional basis only, and their submission is discouraged. The major criteria for publication are clarity, scientific soundness, and advances in knowledge. In compliance with the overwhelmingly prevailing request by the international scientific community, and with respect for eco-compatibility issues, CEM is now published exclusively online.
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