Acute molecular changes in synovial fluid following human knee injury are associated with early clinical outcomes.

Journal article

We investigated whether molecules found to be up-regulated within hours of surgical joint destabilisation in the mouse were also elevated in the analogous human setting of acute knee injury, how this molecular response varied between individuals, and whether it related to patient-reported outcomes in the 3 months after injury.7 candidate molecules were analysed in blood and synovial fluid (SF) of 150 participants with recent structural knee injury at baseline (<8 weeks from injury) and in blood at 14 days and 3 months following baseline. KOOS4 was collected at baseline and 3 months. Assays were by MesoScale Discovery™platform or ELISA, and compared with controls.6/7 molecules were significantly elevated in human synovial fluid immediately after injury: IL-6, MCP-1, MMP-3, TIMP-1, activin-A and TSG-6. There was low-moderate correlation with blood measurements. 3/6 molecules were significantly associated with baseline KOOS4 (those with higher SFIL-6, TIMP-1 or TSG-6 had lower KOOS4 ). These 3, MMP-3 and activin-A were all significantly associated with greater improvement in KOOS over 3 months, adjusting for other relevant factors. Of these, IL-6 alone significantly accounted for the molecular contribution to baseline KOOS4 , and its difference over 3 months.Our findings validate relevant human biomarkers of tissue injury identified in a mouse model. Analysis of SF rather than blood more accurately reflects this response. The response is associated with patient-relevant outcomes over this early period, SF IL-6 acting as a single representative marker. Longitudinal outcomes will determine if these molecules are biomarkers of subsequent disease risk. This article is protected by copyright. All rights reserved.

Authors: Watt, F; Paterson, E; Freidin, A; Kenny, M; Judge, A

• Publication status: In press
• Peer review status: Peer reviewed
• Publisher: Wiley
• Journal: Arthritis and Rheumatology
• Publication date: 2016-03-18
• Acceptance date: 2016-03-03
• DOI: 10.1002/art.39677
• EISSN: 2326-5205
• ISSN: 2326-5191
• Language: English