Cartilage collagen neoepitope c2c and clinical parameters in middle-aged patients with knee problems. Correlations of urinary output of C2C with cartilage lesions, koos values and functional abilities of lower limb

Purpose: Intensive research in the last decade has demonstrated that protein biomarkers are required for different purposes in early osteoarthritis (OA): to detect OA, to prognose its progression, to assess efficacy of intervention, etc. Although several biomarkers have acquired definite position in the field, none of the biomarkers applied up to now can sufficiently discriminate individual or limited number of patients (Labefer, van Spil, 2013). One of the likely ways to proceed is to investigate neoepitopes. A collagen type II neoepitope C2C was developed for this purpose. The aims of the study were to test: (i) the biomarker’s ability to differentiate between patients with and without knee cartilage lesion, (ii) if there is any correlation between urinary C2C output and clinical status of patients with early knee osteoarthritis, (iii) preferable option to express results (ng/mmol of creatinine or pg/ml of urine). Material and methods: We investigated 180 knee OA patients (68 male, 112 female) aged 36-62 (mean 50) yrs. For 112 patients the progression of the knee OA during the past 3 years was available. Standardised radiographs of the tibiofemoral(TF) and patello[[Unsupported Character – Codename ­]]femoral(PF) joints were assessed. Radiographic progression was defined as: (i)presence of osteophytes and/or joint space narrowing (JSN) in subjects with no previous radiographic OA or (ii)increase in their grade. In a subset of 51 patients (25 male, 26 female, aged 32-56 yrs) the degree of cartilage lesion was assessed by an orthopedic surgeon on the Outerbridge (0-IV) and VAS (0-10) scales in the medial femoral, medial tibial and patellofemoral compartments. The clinical status of OA patients was established by KOOS questionnaire (self-assessment) and by four performance tests (up & go, raising from low chair, stairs-stepping, 30 m walk). The immunoassay used was C2C-HUSA™ (IBEX, Canada) that measures the C2C neoepitope fragments present in human urine samples. For statistical data analyses, T-test and Spearman’s rank correlation were used. Results: The uC2C values were significantly higher for patients with tibial or femoral lesion degree 2 or higher both at baseline and 3 yrs after surgery (Fig. 1, B and 3 yrs). Excretion of u-C2C correlated positively with knee symptoms as well as with limitations of everyday and demanding recreative (Sp/Rec) activities (Table 1).Table 1Correlations between urinary C2C and results of KOOS questionnaire in female patientsKOOS subscales, femalesuC2C expressed in pg/ml urinein ng/mmol creatinineKnee symptoms107-0.2670.005-0.380.00005knee pain107-0.2720.005-0.4110.00001limitations in ADL107-0.3210.001-0.4640.0000005limitations in Sp/Rec105-0.4330.000004-0.5531E-09Quality of life107-0.3370.0004-0.5120.00000002 Open table in a new tab Higher output of uC2C correlates with decline of the functional abilities of lower limb. In both cases the correlations were stronger when uC2C was expressed in ng/mmol creatinine (Tables 1, 2).Table 2Correlations between urinary C2C and results of lower limb performance testsPerformance testsValid (N)uC2C expressed in pg/ml urineuC2C expressed in ng/mmol creatinineSpearman (R)p-valueSpearman (R)p-valueUP&GO, sec1070.3040.0010.4150.000009Up from low chair, cm1060.3720.000080.5250.000000008Step up left leg, cm107-0.3540.0001-0.4480.000001Step up right leg, cm107-0.360.0001-0.4840.000000130 m walk, sec1070.2380.0140.4050.00001 Open table in a new tab Conclusions: 1. Significantly higher excreation of uC2C is associated with grade 2+ cartilage lesion in knee joint. 2. Highly significant correlation appears between increased uC2C output and decline in the clinical parameters of the lower limb. 3. The above correlations are stronger when uC2C is expressed in ng/mmol creatinine.