Profiling of plasma extracellular vesicles identifies proteins that strongly associate with patient’s global assessment of disease activity in rheumatoid arthritis
BackgroundRheumatoid 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 asses...
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| Format: | Article |
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2023.1247778/full |
| _version_ | 1797357755782135808 |
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| author | Onno J. Arntz Rogier M. Thurlings Esmeralda N. Blaney Davidson Pascal W. T. C. Jansen Michiel Vermeulen Marije I. Koenders Peter M. van der Kraan Fons A. J. van de Loo |
| author_facet | Onno J. Arntz Rogier M. Thurlings Esmeralda N. Blaney Davidson Pascal W. T. C. Jansen Michiel Vermeulen Marije I. Koenders Peter M. van der Kraan Fons A. J. van de Loo |
| author_sort | Onno J. Arntz |
| collection | DOAJ |
| description | BackgroundRheumatoid 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.MethodsWe 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).ResultsNo 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.ConclusionOur 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. |
| first_indexed | 2024-03-08T14:49:36Z |
| format | Article |
| id | doaj.art-0fdda973c7cd427699c6d95bfaeef970 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-03-08T14:49:36Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Medicine |
| spelling | doaj.art-0fdda973c7cd427699c6d95bfaeef9702024-01-11T04:29:38ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2024-01-011010.3389/fmed.2023.12477781247778Profiling of plasma extracellular vesicles identifies proteins that strongly associate with patient’s global assessment of disease activity in rheumatoid arthritisOnno J. Arntz0Rogier M. Thurlings1Esmeralda N. Blaney Davidson2Pascal W. T. C. Jansen3Michiel Vermeulen4Marije I. Koenders5Peter M. van der Kraan6Fons A. J. van de Loo7Department of Rheumatology, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Rheumatology, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Rheumatology, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Oncode Institute, Radboud University Nijmegen, Nijmegen, NetherlandsDepartment of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Oncode Institute, Radboud University Nijmegen, Nijmegen, NetherlandsDepartment of Rheumatology, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Rheumatology, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Rheumatology, Radboud University Medical Center, Nijmegen, NetherlandsBackgroundRheumatoid 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.MethodsWe 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).ResultsNo 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.ConclusionOur 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.https://www.frontiersin.org/articles/10.3389/fmed.2023.1247778/fullextracellular vesiclesrheumatoid arthritisPGA-VASplasmaproteomicsvitality |
| spellingShingle | Onno J. Arntz Rogier M. Thurlings Esmeralda N. Blaney Davidson Pascal W. T. C. Jansen Michiel Vermeulen Marije I. Koenders Peter M. van der Kraan Fons A. J. van de Loo Profiling of plasma extracellular vesicles identifies proteins that strongly associate with patient’s global assessment of disease activity in rheumatoid arthritis Frontiers in Medicine extracellular vesicles rheumatoid arthritis PGA-VAS plasma proteomics vitality |
| title | Profiling of plasma extracellular vesicles identifies proteins that strongly associate with patient’s global assessment of disease activity in rheumatoid arthritis |
| title_full | Profiling of plasma extracellular vesicles identifies proteins that strongly associate with patient’s global assessment of disease activity in rheumatoid arthritis |
| title_fullStr | Profiling of plasma extracellular vesicles identifies proteins that strongly associate with patient’s global assessment of disease activity in rheumatoid arthritis |
| title_full_unstemmed | Profiling of plasma extracellular vesicles identifies proteins that strongly associate with patient’s global assessment of disease activity in rheumatoid arthritis |
| title_short | Profiling of plasma extracellular vesicles identifies proteins that strongly associate with patient’s global assessment of disease activity in rheumatoid arthritis |
| title_sort | profiling of plasma extracellular vesicles identifies proteins that strongly associate with patient s global assessment of disease activity in rheumatoid arthritis |
| topic | extracellular vesicles rheumatoid arthritis PGA-VAS plasma proteomics vitality |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2023.1247778/full |
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