Biomarker Changes in ACL Deficient Knees Compared with Contralaterals

OBJECTIVES: Introduction: Though outcomes following ACL reconstruction are largely positive, patients’ post-operative recovery is highly variable, and is typically based off generalized timetables derived from population data. In an attempt to individualize prognostic estimates and establish how biomarker concentrations may change with injury, we sampled knee joint synovial fluid from patients with ACL tears with and without associated cartilage injuries and compared biomarker concentrations to samples obtained from the contralateral non-injured knee. METHODS: 480 patients indicated for knee arthroscopy had samples drawn to form a synovial fluid database. If no injury history or symptoms were present in the contralateral knee, samples were drawn as well. For the current study, only patients that had confirmed ACL injury at the time of arthroscopy were included. Associated cartilage injury location, size and depth was documented. Synovial fluid samples were centrifuged, and the concentrations of 20 biomarkers were determined using a multiplex magnetic bead immunoassay. Concentrations were then compared between the three study groups (ACL tear with cartilage injury, ACL tears without cartilage injury, and healthy contralateral knees) using a Welch ANOVA test with pairwise comparisons. RESULTS: The study included samples from 132 knees: 34 ACL tears without cartilage injury (mean age 34.0 years); 28 ACL tears with cartilage injury (mean age 36.3 years), and 72 contralateral knees (41.1 years). ANOVA testing demonstrated significant differences among groups for: MMP-3 (p>001); TIMP-1 (p=.001); TIMP-2 (p=.015); FGF-2 (p=.011); IL-6 (p=.001); and MIP-1b (p=.001). Pairwise comparisons demonstrated no significant differences between ACL tears with, and without cartilage damage, but did show both types of ACL tears had significantly higher concentrations of MMP-3, TIMP-1, IL-6, and MIP-1b than contralaterals. ACL tears without cartilage damage had significantly lower concentrations of TIMP-2 and FGF-2 (13) than contralaterals (Table 1). CONCLUSION: The course from surgery to symptomatic relief and functional improvement following ACL reconstruction is highly variable. Data from the current study demonstrated that cytokine concentrations are significantly different between ACL tears (+/- cartilage damage) and healthy knees. These validated differences can help establish synovial fluid biomarker analysis as a method for injury stratification ultimately providing patient-specific prognostic data.