Association of synovial fluid and urinary C2C-HUSA levels with surgical outcomes post-total knee arthroplasty.

OBJECTIVES: After total knee arthroplasty (TKA), ∼30% of knee osteoarthritis (KOA) patients show little symptomatic improvement. Earlier studies have correlated urinary (u) type 2 collagen C terminal cleavage peptide assay (C2C-HUSA), which detects a fragment of cartilage collagen breakdown, with KOA progression. This study determines whether C2C levels in urine, synovial fluid, or their ratio, are associated with post-surgical outcomes. METHODS: From a large sample of 489 subjects, diagnosed with primary KOA undergoing TKA, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function scores were collected at baseline (time of surgery) and one-year post-TKA. Baseline urine (u) and synovial fluid (sf) were analysed using the IBEX-C2C-HUSA assay, with higher values indicating higher amounts of cartilage degradation. For urine, results were normalised to creatinine. Furthermore, subjects' changes in WOMAC scores were categorised based on percent reduction in pain or improvement in function, compared to baseline, such that >66.7%, >33.3 to ≤66.7%, and ≤33.3% denoted "strong", "moderate" and "mild/worse" responses, respectively. Associations of individual biofluid C2C-HUSA levels, or their ratio, with change in WOMAC pain and function scores up to one-year post-TKA, or category of change, were analysed by linear, logistic, or cumulative odds models. RESULTS: Higher baseline uC2C-HUSA levels or a lower ratio of baseline sfC2C-HUSA to uC2C-HUSA were associated with improvements in WOMAC pain by linear multivariable modelling [odds ratio -0.40 (95% confidence interval -0.76, -0.05) p = 0.03; 0.36 (0.01, 0.71), p = 0.04, respectively], while sfC2C-HUSA alone was not. However, lower ratios of sfC2C-HUSA to uC2C-HUSA were associated with improvements in WOMAC function [1.37 (0.18, 2.55), p = 0.02], while sfC2C-HUSA and uC2C-HUSA alone were not. Lower ratios of sfC2C-HUSA to uC2C-HUSA were also associated with an increased likelihood of a subject being categorised in a group where TKA was beneficial in both univariable [pain, 0.81 (0.68, 0.96), p = 0.02; function, 0.92 (0.85, 0.99), p = 0.035] and multivariable [pain, 0.81 (0.68, 0.97) p = 0.02; function, 0.92 (0.85, 1.00), p = 0.043] ordinal modelling, while sfC2C-HUSA and uC2C-HUSA alone were not. CONCLUSIONS: Overall, ratios of baseline sfC2C-HUSA to uC2C-HUSA, and baseline uC2C-HUSA, may play an important role in studying post-TKA surgical outcomes.

T-cell responses to versican in ankylosing spondylitis.

The objective of our study was to undertake a systematic analysis of the T-cell response to the proteoglycan versican G1-globular domain (VG1) in ankylosing spondylitis (AS) as immunity to VG1 in mice can induce a pathology closely resembling AS. Peripheral blood lymphocytes from 36 AS patients and 33 healthy controls were incubated with recombinant human VG1 in culture for 6 h. T-cell responses were assessed by FACS analyses using mAb against surface expression of the activation marker CD69 and against the intracellular cytokines interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha. T cells activated by exposure to versican were determined by assessing the percentage of CD4+ or CD8+ T cells that were CD69/cytokine double-positive cells as compared to isotype control staining. In the AS patients, exposure to VG1 resulted in increased expression by CD4+ T cells of IFN-gamma in 55.6% of patients and of TNF-alpha in 52.8% of patients. In the controls, only 36.4% of subjects demonstrated an IFN-gamma response and 36.4% demonstrated a TNF-alpha response (P value 0.148, 0.227, respectively). With respect to CD8+ T-cell responses, versican stimulation enhanced IFN-gamma expression in 44.4% of AS patients and 39.4% of controls, and enhanced TNF-alpha response in 50.0% of AS patients and 39.4% of controls (P value 0.620, 0.327, respectively). Although, there was no statistically significant difference in the magnitude of the IFN-γ or TNF secretion by CD4+ T cells and CD8+ T cells between AS and controls, our results demonstrate an enhanced T-cell response to VG1 in AS.