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pmid:38274452
Profiling of plasma extracellular vesicles identifies proteins that strongly associate with patient's global assessment of disease activity in rheumatoid arthritis.
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
Frontiers in medicine · 2023 doi:10.3389/fmed.2023.1247778
Paper
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Experiment
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Data
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Analysis
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Complete file
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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.\nMethods: 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).\nResults: 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.\nConclusion: 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.", "claims": [{"id": "claim-method", "statement": "Correlations of RA-pEV protein levels to clinical parameters were represented by Spearman’s rank correlation coefficient (ρ) and their p values.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38274452", "locator": "sections[12] \"Statistical analysis\" paragraph 2", "quote": "Correlations of RA-pEV protein levels to clinical parameters were represented by Spearman’s rank correlation coefficient (ρ) and their p values."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data presented in the study are deposited in the PRoteomics IDEntifications (PRIDE) Archive database (http://www.ebi.ac.uk/pridel), accession number pxd046058. The numbering of individual pEV donors is available in Supplementary material Table S-1.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38274452", "locator": "sections[19] \"Data availability statement\" paragraph 2", "quote": "The data presented in the study are deposited in the PRoteomics IDEntifications (PRIDE) Archive database (http://www.ebi.ac.uk/pridel), accession number pxd046058. The numbering of individual pEV donors is available in Supplementary material Table S-1."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Remarkably, in both runs, the level of far more RA-pEV proteins correlated positively to PGA-VAS than to either clinical or laboratory parameters.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38274452", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Remarkably, in both runs, the level of far more RA-pEV proteins correlated positively to PGA-VAS than to either clinical or laboratory parameters."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Remarkably, in both runs, the level of far more RA-pEV proteins correlated positively to PGA-VAS than to either clinical or laboratory parameters.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:38274452"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": [], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38274452", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fmed.2023.1247778", "sha256": "sha256:f2f2a29e7f9cddc5af07ee4b3856551d14ca98520f1861d1866d17c8597f5ca6", "bytes": 42305, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fmed.2023.1247778", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10808582", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}], "gaps": []}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": null, "specific": null, "label": "Spearman’s rank correlation coefficient (ρ)", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Correlations of RA-pEV protein levels to clinical parameters were represented by Spearman’s rank correlation coefficient (ρ) and their p values."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "blocked", "tier": "R4", "blocking_axis": "data", "blocked_on": "data:accession_absent", "axes": {"method": {"tier": "R4", "expressible": false, "required_operations": [], "missing_operations": [], "basis": "The reader quoted the method the paper names (Spearman’s rank correlation coefficient (ρ)), but the corpus's method extractor could not map it onto a DSL operation, so the method is published but not expressible."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R4", "reachable": false, "accessions": ["pxd046058"], "resolved_accessions": [], "statements": ["The data presented in the study are deposited in the PRoteomics IDEntifications (PRIDE) Archive database (http://www.ebi.ac.uk/pridel), accession number pxd046058. The numbering of individual pEV donors is available in Supplementary material Table S-1."], "basis": "The paper names pxd046058, but the accession does not resolve in the repository (no reason recorded), so the data cannot be reached from here. 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