Use of extracellular vesicles as biomarkers for the diagnosis of Rheumatoid Arthritis: Systematic Review and Meta-Analysis

Rheumatoid arthritis (RA) is a multifactorial autoimmune inflammatory disease with a polyarticular pattern, characterized by joint stiffness, chronic pain, and synovitis mainly affecting the small proximal synovial joints. The repercussions of this disease are systemic, and there may be extra-articular and constitutional manifestations. Regarding the diagnosis of RA, clinical biomarkers are currently used which have limitations, mainly regarding sensitivity and specificity. Therefore, exosomes are being studied as promising biomarkers for more efficient diagnosis and monitoring of RA. Exosomes are extracellular vesicles (EVs) secreted by almost all cell types physiologically and pathologically, playing a major role in RA. Therefore, this research aims to evaluate, by a systematic review, the effectiveness of EVs as a biomarker for the diagnosis of RA. To this end, the study will be conducted based on the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The electronic literature search will be carried out using the PubMed/MEDLINE, Scopus, and Cochrane Library databases, which will be carried out until March 2025 to answer the PICO question: “Would the use of extracellular vesicles as a biomarker be more efficient than the markers used currently used for the diagnosis of rheumatoid arthritis?” Efficacy in diagnosis will be considered the primary outcome. The biological material used as the source of EVs and the method for biomarkers will be included in the secondary outcomes. After selecting the articles and extracting the data, they will be subjected to bias analysis and meta-analysis. It is expected to determine the effectiveness of EVs as a biomarker for the diagnosis of RA.