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Profiling of plasma extracellular vesicles identifies proteins that strongly associate with patient's global assessment of disease activity in rheumatoid arthritis.
Arntz, Onno J; Thurlings, Rogier M; Blaney Davidson, Esmeralda N; Jansen, Pascal W T C; Vermeulen, Michiel; Koenders, Marije I; van der Kraan, Peter M; van de Loo, Fons A J.
Afiliación
  • Arntz OJ; Department of Rheumatology, Radboud University Medical Center, Nijmegen, Netherlands.
  • Thurlings RM; Department of Rheumatology, Radboud University Medical Center, Nijmegen, Netherlands.
  • Blaney Davidson EN; Department of Rheumatology, Radboud University Medical Center, Nijmegen, Netherlands.
  • Jansen PWTC; Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Oncode Institute, Radboud University Nijmegen, Nijmegen, Netherlands.
  • Vermeulen M; Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Oncode Institute, Radboud University Nijmegen, Nijmegen, Netherlands.
  • Koenders MI; Department of Rheumatology, Radboud University Medical Center, Nijmegen, Netherlands.
  • van der Kraan PM; Department of Rheumatology, Radboud University Medical Center, Nijmegen, Netherlands.
  • van de Loo FAJ; Department of Rheumatology, Radboud University Medical Center, Nijmegen, Netherlands.
Front Med (Lausanne) ; 10: 1247778, 2023.
Article en En | MEDLINE | ID: mdl-38274452
ABSTRACT

Background:

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovial inflammation and cartilage/bone damage. Intercellular messengers such as IL-1 and TNF play a crucial role in the pathophysiology of RA but have limited diagnostic and prognostic values. Therefore, we assessed whether the protein content of the recently discovered extracellular vesicles (EVs), which have gained attention in the pathogenesis of RA, correlates with disease activity parameters in RA patients.

Methods:

We identified and quantified proteins in plasma-derived EVs (pEVs), isolated by size exclusion chromatography from 17 RA patients by mass spectrophotometry (MS). Quantified protein levels were correlated with laboratory and clinical parameters and the patient's own global assessment of their disease activity (PGA-VAS). In a second MS run, the pEV proteins of nine other RA patients were quantified and compared to those from nine healthy controls (HC).

Results:

No differences were observed in the concentration, size, and protein content of pEVs from RA patients. Proteomics revealed >95% overlapping proteins in RA-pEVs, compared to HC-pEVs (data are available via ProteomeXchange with identifier PXD046058). Remarkably, in both runs, the level of far more RA-pEV proteins correlated positively to PGA-VAS than to either clinical or laboratory parameters. Interestingly, all observed PGA-VAS positively correlated RA-pEV proteins were associated with the actin-cytoskeleton linker proteins, ezrin, and moesin.

Conclusion:

Our observation suggests that PGA-VAS (loss of vitality) may have a different underlying pathological mechanism in RA, possibly related to enhanced muscle actin-cytoskeleton activity. Furthermore, our study contributes to the growing awareness and evidence that pEVs contain valuable biomarkers for diseases, with added value for RA patients.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Risk_factors_studies Idioma: En Revista: Front Med (Lausanne) Año: 2023 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Risk_factors_studies Idioma: En Revista: Front Med (Lausanne) Año: 2023 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Suiza