Small extracellular vesicle cargo as biomarkers in autoimmune rheumatic diseases: a systematic review

Increasing evidence has shown the role of small extracellular vesicles (sEVs) in autoimmune rheumatic diseases (ARDs). This systematic literature review aims to evaluate the role of sEVs as biomarkers in ARDs, focusing on their molecular cargo and their utility for disease diagnosis, monitoring, and treatment response. A systematic search was conducted in MEDLINE/PubMed and Scopus from inception until July 2025, using the search terms; [(small extracellular vesicles) or exosomes) and ((rheumatic disease) or (rheumatoid arthritis) or (psoriatic arthritis) or (axial spondylarthritis) or (ankylosing spondylitis) or (systemic lupus erythematosus) or (Sjögren's syndrome) or scleroderma or (systemic sclerosis) or myositis or polymyositis)]. Eligible studies were those reporting on sEV isolation from patient samples and comparing it with healthy individuals or controls with non-inflammatory conditions. The initial search yielded 1593 results, and 46 studies met the inclusion criteria. Literature reviews revealed that miRNAs and long non-coding (lnc)RNAs isolated from sEVs might serve as potential biomarkers for disease activity and treatment response in ARDs, mainly in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In addition, sEV miRNA-21 and miRNA-146a have been often described in studies in SLE patients, indicating their potential role in differentiating SLE from healthy individuals. Although proteomic studies identified disease-specific proteins within sEVs, there is no consensus among the limited studies reporting sEV proteins. Although numerous studies have examined the role of sEVs in ARDs, there is a lack of consensus in the findings. Further research using well-standardized methodologies is needed to ensure reliable and reproducible results. PROSPERO 2025 CRD420250646438. Available from https://www.crd.york.ac.uk/PROSPERO/view/CRD420250646438 .