Di Lorenzo Biagio, Zoroddu Stefano, Mangoni Arduino A, Paliogiannis Panagiotis, Erre Gian Luca, Carru Ciriaco, Zinellu Angelo
Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
Department of Medicine and Surgery, LUM University, Casamassima, Italy.
Eur J Clin Invest. 2025 May;55(5):e14365. doi: 10.1111/eci.14365. Epub 2024 Nov 28.
Rheumatic diseases (RDs) include a broad group of disabling conditions with different phenotypes, from autoimmune to autoinflammatory, degenerative, metabolic or mixed manifestations. With the continuous efforts to identify therapeutic targets for new biologic drugs to treat overt clinical manifestations, research is also focusing on the discovery of new biomarkers to diagnose and manage early disease stages. In this context, we conducted a systematic review and meta-analysis of Fetuin-A (FtA), a glycoprotein synthesized by the liver that participates in several biological processes and has been proposed as a biomarker for several disorders, including rheumatoid arthritis.
A systematic search in PubMed, Scopus and Web of Science, from inception to the 24th of August 2024, led to the identification of 13 manuscripts from 219 records; six additional studies were identified through reference hand-search, for a total of 19 studies.
There was a significant decrease in FtA concentrations in RD patients (standardized mean difference, SMD = -.91; 95% CI -1.43 to -.39, p = .001), with no substantial contribution from any individual study nor publication bias. The effect size was significantly associated with erythrocyte sedimentation rate, various lipid fractions, geographical area of study conduction, study design and specific type of RD.
In conclusion, our study identified significant reductions in FtA concentrations in RD patients versus healthy controls. These alterations were significantly associated with specific study and patient characteristics. Further research is required to identify the exact pathophysiological mechanisms underlying these alterations and the possible utility of measuring FtA for the diagnosis and management of RDs.
风湿性疾病（RDs）包括一大类致残性疾病，具有不同的表型，从自身免疫性到自身炎症性、退行性、代谢性或混合性表现。在不断努力确定用于治疗明显临床表现的新型生物药物治疗靶点的同时，研究也聚焦于发现新的生物标志物以诊断和管理疾病早期阶段。在此背景下，我们对胎球蛋白-A（FtA）进行了一项系统评价和荟萃分析，FtA是一种由肝脏合成的糖蛋白，参与多种生物学过程，并已被提议作为包括类风湿关节炎在内的多种疾病的生物标志物。
在PubMed、Scopus和Web of Science数据库中进行系统检索，检索时间从建库至2024年8月24日，从219条记录中筛选出13篇手稿；通过参考文献手工检索又确定了6项研究，共计19项研究。
RD患者的FtA浓度显著降低（标准化均值差，SMD = -0.91；95%可信区间-1.43至-0.39，p = 0.001），没有任何一项单独研究有实质性贡献，也不存在发表偏倚。效应大小与红细胞沉降率、各种血脂成分、研究开展的地理区域、研究设计以及RD的具体类型显著相关。
总之，我们的研究发现RD患者的FtA浓度相对于健康对照者显著降低。这些改变与特定的研究和患者特征显著相关。需要进一步研究以确定这些改变背后的确切病理生理机制以及测量FtA在RD诊断和管理中的可能效用。
