TSG-6 activity as a novel biomarker of progression in knee osteoarthritis

Abstract

Objective To establish whether there is an association between TSG-6 activity and osteoarthritis (OA) progression. Design TSG-6 activity was determined in 132 synovial fluids from patients with OA of the knee, using a novel quantitative TSG-6 activity assay. The association between TSG-6 activities at baseline and four distinct disease progression states, determined at three-year follow-up, was analyzed using logistic regression. Results There was a statistically significant relationship between TSG-6 activity at baseline and all OA progression states over a three-year period. Patient knees with TSG-6 activities in the top 10th percentile, compared to the median activity, had an odds ratio (OR) of at least 7.86 (confidence interval (CI) [3.2, 20.5]) for total knee arthroplasty (TKA) within three years, and of at least 5.20 (CI [1.8, 13.9]) after adjustment for confounding factors. Receiver operating characteristic (ROC) analysis for knee arthroplasty yielded a cut-off point of 13.3 TSG-6 activity units/ml with the following parameters: area under the curve 0.90 (CI [0.804, 0.996]), sensitivity 0.91 (CI [0.59, 0.99]), specificity 0.82 (CI [0.74, 0.88]) and a negative predictive value (NPV) of 0.99 (CI [0.934, 0.994]). Conclusion The TSG-6 activity is a promising independent biomarker for OA progression. Given the high NPV, this assay may be particularly suitable for identifying patients at low risk of rapid disease progression and to assist in the timing of arthroplasty.

Insights into osteoarthritis progression revealed by analyses of both knee tibiofemoral compartments

“…TNFAIP6 (tumor necrosis factor, alpha-induced protein 6) is a third example of a gene whose role in OA progression is unclear. TNFAIP6 is a secretory protein that contains a hyaluronan-binding domain; increased levels of this protein are found in the synovial fluid of patients with OA and OA progression [24]. Therefore, the present study provides strong proof of the concept that this model system recapitulates states of OA progression and provides disease-relevant molecular signatures.…”

“…Of the eight genes that could be validated as disease associated in both MOA and LOA samples, 7 genes have been implicated in the organization of cartilage extracellular matrix, cartilage development or OA pathogenesis [18–24]. The single exception, the PDE3B gene, has not been implicated previously in OA.…”

Nuclear Magnetic Resonance Insight into the Multiple Glycosaminoglycan Binding Modes of the Link Module from Human TSG-6

“…HC•HA complexes are also formed at sites of inflammation (e.g. in the synovial fluids from arthritis sufferers 27 ), where the HC transferase activity of TSG-6 has been found to be predictive of osteoarthritis severity and the need for joint replacement 28 . The transfer of HCs onto HA likely involves the interaction of TSG-6 with the CS chain of IαI, i.e.…”

Knee pain, knee injury, knee osteoarthritis & work

“…Using this overall hypothesis, a number of potential biomarkers have been considered. For example; peptides representative of clusterin and lubricin in addition to novel markers such as TSG-6 have all shown reasonable potential in recent studies investigating the role of viable biomarkers in OA [31,32] Urinary biomarkers may also prove to be useful: C-terminal telopeptide (uCTX-II) has been shown in a recent meta-analysis to be an informative biomarker for likelihood of progression to OA [33] Larger scale clinical correlation of biomarker validity is the next step and this ultimately aims to provide a unique model of predicting and detecting OA early in the disease course. The relevance of detecting very early signs of osteoarthritis of the knee in the future is likely to be dependant on available targeted treatments.…”