Do microenvironmental changes in degenerative disc disease reflect in systemic circulation? A proteomic investigation.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41372752", "kind": "science-record", "revision": 3, "content_hash": "sha256:92221d1f735fc911c4afc87c7c85f6f9105392f131059601584eac510707ebed", "created_at": "2026-11-01T20:31:23Z", "updated_at": "2026-11-01T22:15:09Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Do microenvironmental changes in degenerative disc disease reflect in systemic circulation? A proteomic investigation.", "doi": "10.1186/s12014-025-09563-3", "pmid": "41372752", "authors": ["Sharon Miracle Nayagam", "Narmatha Devi Palraj", "Murugesh Eswaran", "Ganesh Selvaraj", "Sunmathi Rajendran", "Karthik Ramachandran", "Divya Arunachalam", "Chitraa Tangavel", "Srivijay Anand K S", "Muthurajan Raveendran", "Shanmuganathan Rajasekaran"], "journal": "Clinical proteomics", "year": 2025, "abstract": "BACKGROUND: The complement system plays a crucial role in immune regulation and inflammation, contributing to intervertebral disc degeneration (IDD) pathogenesis. While tissue-specific complement activation in degenerated discs is well-documented, its systemic expression in degenerative disc disease (DDD) plasma remains unclear.\nMETHODS: This study employed high-throughput mass spectrometry to analyze the plasma and tissue proteomes of 40 DDD patients, comprising of Modic change (MC) and non-Modic change (NMC) patients, alongside 20 healthy volunteers (HV). Only plasma and no plasma-matched tissue samples were collected from HV group.\nRESULTS: Proteomic analysis identified 707 proteins in DDD plasma and 655 in HV plasma, with 508 common. Complement and coagulation cascades were enriched, with 46 complement proteins identified. The DDD-plasma group exhibited upregulation of most complement proteins, except for C1q complex (1.38-fold) and Complement Factor D (CFD, 0.64-fold), alongside slight downregulation of vitronectin (VTN), clusterin (CLU), and complement C8G. Elevated C-reactive protein (CRP) levels were observed in DDD-plasma, indicating systemic inflammation. Correlation analysis revealed weak associations between plasma and tissue complement protein levels, suggesting potential regulatory mechanisms.\nCONCLUSION: Our study reveals that systemic complement alterations in DDD, supporting their potential as blood-based biomarkers reflecting localized disc pathology. Further validation in larger cohorts across different disease stages is needed to explore their diagnostic and therapeutic implications. Data are available via ProteomeXchange with identifier PXD063403.", "claims": [{"id": "claim-method", "statement": "Correlation analysis, as shown in Fig. 9b, revealed weak positive and negative correlations (± 0.50) between plasma and tissue expression levels.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41372752", "locator": "sections[17] \"Association of complement expression between DDD-tissue and DDD-plasma\" paragraph 2", "quote": "Correlation analysis, as shown in Fig. 9b, revealed weak positive and negative correlations (± 0.50) between plasma and tissue expression levels."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [63] partner repository with the dataset identifier PXD063403. 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A DOI has not yet been assigned."}], "state": "complete"}, {"id": "claim-target-result", "statement": "C4B showed the strongest reported moderate positive correlation between plasma and tissue complement-protein levels (r = 0.43, p = 8.74E-18), whereas the overall analysis showed only weak positive and negative plasma–tissue correlations.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41372752", "locator": "sections[17] \"Association of complement expression between DDD-tissue and DDD-plasma\" paragraph 5", "quote": "Among the complement proteins, C4B (r = 0.43, p = 8.74E-18), CFHR1 (r = 0.37, p = 6.99E-08), and F5 (r = 0.33, p = 1.78E-10) showed moderate positive correlations between plasma and tissue levels."}, {"asset": "source:pmid:41372752", "locator": "sections[17] \"Association of complement expression between DDD-tissue and DDD-plasma\" paragraph 2", "quote": "Correlation analysis, as shown in Fig. 9b, revealed weak positive and negative correlations (± 0.50) between plasma and tissue expression levels."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "C4B showed the strongest reported moderate positive correlation between plasma and tissue complement-protein levels (r = 0.43, p = 8.74E-18), whereas the overall analysis showed only weak positive and negative plasma–tissue correlations.", "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:41372752"], "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": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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