Micro-RNA content of circulating extracellular vesicles in early rheumatoid arthritis as biomarkers and mediators of methotrexate efficacy.

Autor:	Maunder D; Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, UK., Brown PM; Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, UK.; Musculoskeletal Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK., Barron-Millar B; Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, UK., Lendrem DW; Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, UK., Naamane N; Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, UK., Macdonald J; Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, UK., Wang XN; Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, UK., Isaacs JD; Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, UK.; Musculoskeletal Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK., Anderson AE; Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, UK., Morgan AW; School of Medicine, University of Leeds, Leeds, UK.; Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK., Crossland RE; Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, UK., Mackie SL; School of Medicine, University of Leeds, Leeds, UK.; Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK., Pratt AG; Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, UK.; Musculoskeletal Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK.
Jazyk:	angličtina
Zdroj:	Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2024 Aug 01; Vol. 63 (8), pp. 2259-2267.
DOI:	10.1093/rheumatology/kead569
Abstrakt:	Objectives: Extracellular vesicles (EVs) are abundant in body fluids, contributing to intercellular signalling by transferring cargo that includes microRNAs (miRs)-themselves implicated in pathobiology. For the first time we evaluated the potential of EV miRs to contribute diagnostic information in early RA, predict methotrexate (MTX) efficacy or shed light on the drug's mechanism of action. Methods: Seven hundred and ninety-eight miRs isolated from serum-derived EVs of 46 patients with untreated RA, 23 with untreated polymyalgia rheumatica (PMR; inflammatory disease control group) and 12 in whom significant inflammatory disease had been excluded (non-inflammatory controls; NICs) were profiled (NanoString); the same measurements were made for RA patients after 6 months' MTX treatment. Analyses took multiple testing into account. Results: Twenty-eight EV miRs were robustly differentially expressed between early RA (but not PMR) patients and NICs after correction for age and sex, suggesting discriminatory value. Cross-validated partial least squares-discriminant analysis also indicated the predictive potential of a distinct baseline EV miR signature with respect to MTX-induced remission at 6 months. The change in expression of 13 miRs over the course of MTX treatment differed significantly between responders and non-responders, and four of those exhibiting increased relative abundance amongst responders have known roles in regulating the pathogenic potential of synovial fibroblasts, namely miR-212-3p, miR-338-5p, miR-410-3p and miR-537. Conclusion: Our data highlight the potential of serum EV miRs as diagnostic and therapeutic biomarkers, highlighting a novel potential mechanism by which MTX may exert its therapeutic effect in early RA that warrants further investigation. (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)
Databáze:	MEDLINE
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