Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
Discipline of Clinical Pharmacology, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia.
Front Immunol. 2024 Jun 14;15:1369284. doi: 10.3389/fimmu.2024.1369284. eCollection 2024.
The identification of novel, yet easily measurable biomarkers of inflammation and oxidative stress might assist in the diagnosis and management of patients with rheumatic diseases (RDs). We conducted a systematic review and meta-analysis of studies investigating the circulating concentrations of bilirubin, the end product of heme metabolism and a potent endogenous antioxidant with anti-inflammatory properties, in patients with RDs and healthy controls. The electronic databases PubMed, Scopus, and Web of Science were searched from inception to 31 December 2023 for relevant articles. We evaluated the risk of bias and the certainty of evidence using the Joanna Briggs Checklist and the Grades of Recommendation, Assessment, Development, and Evaluation Working Group system, respectively. In 17 eligible studies, all with low risk of bias, compared to controls, patients with RDs had significantly lower concentrations of total bilirubin (standard mean difference, SMD=-0.68, 95% CI -0.91 to -0.44, p<0.001; I = 92.5%, p<0.001; low certainty of evidence), direct (conjugated) bilirubin (SMD=-0.67, 95% CI -0.92 to -0.41, p<0.001; I = 81.7%, p<0.001; very low certainty of evidence), and the active antioxidant and anti-inflammatory indirect (unconjugated) form of bilirubin (SMD=-0.71, 95% CI -1.18 to -0.24, p=0.003; I = 95.1%, p<0.001; very low certainty of evidence). The results of the meta-analysis were stable in sensitivity analysis. In meta-regression, there were no significant associations between the SMD of total bilirubin and several clinical and demographic characteristics, including age, male to female ratio, number of participants, liver enzymes and erythrocyte sedimentation rate. In subgroup analysis, the SMD of total bilirubin was significant across a range of RDs, including rheumatoid arthritis, systemic lupus erythematosus, primary Sjögren syndrome, and myositis. Therefore, the results of our systematic review and meta-analysis suggests that the reductions in bilirubin concentrations observed in patients with RDs reflect a state of impaired antioxidant and anti-inflammatory defence due to bilirubin consumption and highlight the promising role of this endogenous product as a biomarker of RDs.
https://www.crd.york.ac.uk/prospero/, identifier CRD42023500649.
鉴定新的、易于测量的炎症和氧化应激生物标志物，可能有助于风湿性疾病（RDs）患者的诊断和管理。
我们对研究胆红素循环浓度的研究进行了系统评价和荟萃分析，胆红素是血红素代谢的终产物，是一种具有抗炎特性的强效内源性抗氧化剂。我们检索了从成立到 2023 年 12 月 31 日的电子数据库 PubMed、Scopus 和 Web of Science，以获取相关文章。我们分别使用 Joanna Briggs 清单和 Grades of Recommendation, Assessment, Development, and Evaluation 工作组系统评估了偏倚风险和证据质量。在 17 项符合条件的研究中，所有研究的偏倚风险均较低，与对照组相比，RDs 患者的总胆红素浓度显著降低（标准均数差，SMD=-0.68，95%置信区间-0.91 至-0.44，p<0.001；I=92.5%，p<0.001；证据质量低），直接（结合）胆红素（SMD=-0.67，95%置信区间-0.92 至-0.41，p<0.001；I=81.7%，p<0.001；证据质量极低），以及活性抗氧化剂和抗炎性间接（非结合）胆红素形式（SMD=-0.71，95%置信区间-1.18 至-0.24，p=0.003；I=95.1%，p<0.001；证据质量极低）。荟萃分析结果在敏感性分析中稳定。在荟萃回归中，总胆红素 SMD 与年龄、男女比例、参与者数量、肝酶和红细胞沉降率等多个临床和人口统计学特征之间无显著关联。在亚组分析中，RDs 包括类风湿关节炎、系统性红斑狼疮、原发性干燥综合征和肌炎，总胆红素 SMD 均有显著差异。因此，我们的系统评价和荟萃分析结果表明，RDs 患者胆红素浓度降低反映了由于胆红素消耗导致抗氧化和抗炎防御受损的状态，并强调了这种内源性产物作为 RDs 生物标志物的有前途的作用。
