Discipline of Clinical Pharmacology, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia.
Department of Clinical Pharmacology, Flinders Medical Centre, Southern Adelaide Local Health Network, Adelaide, SA, Australia.
Front Immunol. 2023 Sep 18;14:1271383. doi: 10.3389/fimmu.2023.1271383. eCollection 2023.
Novel biomarkers of inflammation and oxidative stress might enhance the early recognition, management, and clinical outcomes of patients with rheumatic diseases (RDs). We assessed the available evidence regarding the pathophysiological role of neopterin, the oxidation product of 7,8-dihydroneopterin, a pteridine generated in macrophages activated by interferon-γ, by conducting a systematic review and meta-analysis of studies reporting its concentrations in biological fluids in RD patients and healthy controls.
We searched electronic databases for relevant articles published between inception and 31 August 2023. The risk of bias and the certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and the Grades of Recommendation, Assessment, Development and Evaluation Working Group system, respectively.
In 37 studies, when compared to healthy controls, RD patients had significantly higher concentrations of neopterin both in plasma or serum (standard mean difference, SMD=1.31, 95% CI 1.01 to 1.61; p<0.001; moderate certainty of evidence) and in the urine (SMD=1.65, 95% CI 0.86 to 2.43, p<0.001; I = 94.2%, p<0.001; low certainty of evidence). The results were stable in sensitivity analysis. There were non-significant associations in meta-regression and subgroup analysis between the effect size and age, male to female ratio, year of publication, sample size, RD duration, C-reactive protein, erythrocyte sedimentation rate, specific type of RD, presence of connective tissue disease, analytical method used, or biological matrix investigated (plasma . serum). By contrast, the effect size was significantly associated with the geographical area in studies assessing serum or plasma and with the type of RD in studies assessing urine.
Pending additional studies that also focus on early forms of disease, our systematic review and meta-analysis supports the proposition that neopterin, a biomarker of inflammation and oxidative stress, can be useful for the identification of RDs. (PROSPERO registration number: CRD42023450209).
PROSPERO, identifier CRD42023450209.
新型炎症和氧化应激生物标志物可能增强对风湿性疾病（RDs）患者的早期识别、管理和临床结局。我们通过系统评价和荟萃分析报告了 RD 患者和健康对照者生物体液中新型蝶呤（由干扰素-γ激活的巨噬细胞产生的 7,8-二氢新蝶呤的氧化产物）浓度的研究，评估了其在病理生理学中的作用的现有证据。
我们搜索了电子数据库，以获取截至 2023 年 8 月 31 日发表的相关文章。使用 Joanna Briggs 研究所批判性评价清单和推荐、评估、发展和评估工作组系统分别评估了偏倚风险和证据质量。
在 37 项研究中，与健康对照组相比，RD 患者的血浆或血清（标准均数差，SMD=1.31，95%置信区间 1.01 至 1.61；p<0.001；证据质量为中度）和尿液（SMD=1.65，95%置信区间 0.86 至 2.43，p<0.001；I=94.2%，p<0.001；证据质量低）中新型蝶呤浓度明显更高。敏感性分析结果稳定。元回归和亚组分析表明，效应大小与年龄、男女比例、发表年份、样本量、RD 持续时间、C 反应蛋白、红细胞沉降率、特定类型的 RD、结缔组织疾病的存在、使用的分析方法或研究的生物基质（血浆. 血清）之间无显著相关性。相比之下，在评估血清或血浆的研究中，效应大小与研究地点显著相关，在评估尿液的研究中，与 RD 类型显著相关。
在进一步关注疾病早期形式的研究中，我们的系统评价和荟萃分析支持炎症和氧化应激的生物标志物新型蝶呤可用于识别 RDs 的观点。（PROSPERO 注册号：CRD42023450209）。
PROSPERO，注册号 CRD42023450209。
