Synovial fluid fingerprinting in end-stage knee osteoarthritis: a novel biomarker concept

Bibliographic Details
Title: Synovial fluid fingerprinting in end-stage knee osteoarthritis: a novel biomarker concept
Authors: Chethan Jayadev, Philippa Hulley, Catherine Swales, Sarah Snelling, Gary Collins, Peter Taylor, Andrew Price
Source: Bone & Joint Research, Vol 9, Iss 9, Pp 623-632 (2020)
Publisher Information: The British Editorial Society of Bone & Joint Surgery, 2020.
Publication Year: 2020
Collection: LCC:Diseases of the musculoskeletal system
Subject Terms: osteoarthritis, biomarker, machine learning, Diseases of the musculoskeletal system, RC925-935
More Details: Aims: The lack of disease-modifying treatments for osteoarthritis (OA) is linked to a shortage of suitable biomarkers. This study combines multi-molecule synovial fluid analysis with machine learning to produce an accurate diagnostic biomarker model for end-stage knee OA (esOA). Methods: Synovial fluid (SF) from patients with esOA, non-OA knee injury, and inflammatory knee arthritis were analyzed for 35 potential markers using immunoassays. Partial least square discriminant analysis (PLS-DA) was used to derive a biomarker model for cohort classification. The ability of the biomarker model to diagnose esOA was validated by identical wide-spectrum SF analysis of a test cohort of ten patients with esOA. Results: PLS-DA produced a streamlined biomarker model with excellent sensitivity (95%), specificity (98.4%), and reliability (97.4%). The eight-biomarker model produced a fingerprint for esOA comprising type IIA procollagen N-terminal propeptide (PIIANP), tissue inhibitor of metalloproteinase (TIMP)-1, a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4), monocyte chemoattractant protein (MCP)-1, interferon-γ-inducible protein-10 (IP-10), and transforming growth factor (TGF)-β3. Receiver operating characteristic (ROC) analysis demonstrated excellent discriminatory accuracy: area under the curve (AUC) being 0.970 for esOA, 0.957 for knee injury, and 1 for inflammatory arthritis. All ten validation test patients were classified correctly as esOA (accuracy 100%; reliability 100%) by the biomarker model. Conclusion: SF analysis coupled with machine learning produced a partially validated biomarker model with cohort-specific fingerprints that accurately and reliably discriminated esOA from knee injury and inflammatory arthritis with almost 100% efficacy. The presented findings and approach represent a new biomarker concept and potential diagnostic tool to stage disease in therapy trials and monitor the efficacy of such interventions.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2046-3758
Relation: https://doaj.org/toc/2046-3758
DOI: 10.1302/2046-3758.99.BJR-2019-0192.R1
Access URL: https://doaj.org/article/ce3cc22b5f6a48819efcbe5b547bc851
Accession Number: edsdoj.3cc22b5f6a48819efcbe5b547bc851
Database: Directory of Open Access Journals
More Details
ISSN:20463758
DOI:10.1302/2046-3758.99.BJR-2019-0192.R1
Published in:Bone & Joint Research
Language:English