The assessment of cartilage degradation in vivo: development of an immunoassay for the measurement in body fluids of type II collagen cleaved by collagenases.
ABSTRACT A monoclonal antibody has been developed which recognizes a neoepitope in type II collagen which is generated by the intrahelical cleavage of collagenases. Antibody reactivity is directed at the carboxyl-terminus of the TCA or 3/4 piece of the degraded alpha1(II) chain. Reactivity is dependent upon hydroxylation of proline. Evidence is provided suggesting that epitope binding involves the recognition of a conformational neoepitope. Using an ELISA, we show that this neoepitope can be detected in the urines and sera of nonarthritic persons and patients with rheumatoid arthritis (RA). An increased content is observed in the sera and urines of patients. The assay may be of value in studying cartilage type II degradation both in vitro and in vivo such as in those with arthritis.
Article: Biochemical markers of ongoing joint damage in rheumatoid arthritis--current and future applications, limitations and opportunities.[show abstract] [hide abstract]
ABSTRACT: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease associated with potentially debilitating joint inflammation, as well as altered skeletal bone metabolism and co-morbid conditions. Early diagnosis and aggressive treatment to control disease activity offers the highest likelihood of preserving function and preventing disability. Joint inflammation is characterized by synovitis, osteitis, and/or peri-articular osteopenia, often accompanied by development of subchondral bone erosions, as well as progressive joint space narrowing. Biochemical markers of joint cartilage and bone degradation may enable timely detection and assessment of ongoing joint damage, and their use in facilitating treatment strategies is under investigation. Early detection of joint damage may be assisted by the characterization of biochemical markers that identify patients whose joint damage is progressing rapidly and who are thus most in need of aggressive treatment, and that, alone or in combination, identify those individuals who are likely to respond best to a potential treatment, both in terms of limiting joint damage and relieving symptoms. The aims of this review are to describe currently available biochemical markers of joint metabolism in relation to the pathobiology of joint damage and systemic bone loss in RA; to assess the limitations of, and need for additional, novel biochemical markers in RA and other rheumatic diseases, and the strategies used for assay development; and to examine the feasibility of advancement of personalized health care using biochemical markers to select therapeutic agents to which a patient is most likely to respond.Arthritis research & therapy 04/2011; 13(2):215. · 4.27 Impact Factor
Article: The relation between cartilage biomarkers (C2C, C1,2C, CS846, and CPII) and the long-term outcome of rheumatoid arthritis patients within the CAMERA trial.[show abstract] [hide abstract]
ABSTRACT: The aim of this study was to investigate whether serum biomarker levels of C2C, C1,2C, CS846, and CPII can predict the long-term course of disease activity and radiographic progression early in the disease course of rheumatoid arthritis (RA). In patients in the CAMERA trial, levels of biomarkers were evaluated at baseline and after 1 year of treatment. Relations of (changes in) biomarker values with the mean yearly radiographic progression rate and mean disease activity over a 5-year period were evaluated by using regression analysis. The added predictive value of biomarkers over established predictors for long-term outcome was analyzed by multiple linear regression analysis. Of 133 patients, serum samples were available at baseline and after 1 year of treatment. In the regression analysis C1,2C at baseline, the change in C2C, C1,2C, and the sum of the standardized changes in C2C + C1,2C scores were statistically significantly associated with the mean yearly radiographic progression rate; the change in CPII was associated with the mean disease activity over 5 years of treatment. In the multiple linear regression analysis, only the change in C1,2C was of added predictive value (P = 0.004) for radiographic progression. Explained variances of models for radiographic progression and disease activity were low (0.28 and 0.34, respectively), and the biomarkers only marginally improved the explained variance. The change in C1,2C in the first year after onset of RA has a small added predictive value for disease severity over a 5-year period, but the predictive value of this biomarker combined with current predictive factors is too small to be of use for individual patients.Arthritis research & therapy 05/2011; 13(3):R70. · 4.27 Impact Factor
Article: Early effect of hyaluronic acid intra-articular injections on serum and urine biomarkers in patients with knee osteoarthritis: An open-label observational prospective study.[show abstract] [hide abstract]
ABSTRACT: The aim of the study was to investigate the effect of hyaluronic acid (HA) intra articular injections (IA) on osteoarthritis (OA) biomarkers in patients with knee OA. Prospective open label study. Fifty-one patients with unilateral symptomatic K-OA received IA injections of 2mL of HA on days (D) 1, 7, 14 and were followed 3 months. At D-15 patients were examined and X-rays performed, to exclude patients with bilateral K-OA, or those with more than three symptomatic OA joints. From 15 days (D-15) before the first injection to D90 concomitant therapies were unchanged. Walking pain (WP) on VAS was obtained at each visit. Urine (U) and serum (S) samples were obtained at D-15, D1, D30, and D90. S-C2C, S-Cartilage oligomeric matrix protein, S-HA, S-CS 846 epitope, S-type II collagen propeptide, and U-type II collagen C telopeptide (U-CTX II/creatinin) were assayed. Predictive factors of response were analyzed using logistic regression. Correlations between variables were obtained using Spearman test. Forty-five patients were analyzed. Between D-15 and D1 there was no difference for any biomarkers At D1, WP (SD) was correlated with U-CTX II/creat (p = 0.006). Between D1 and D90: U-CTX II/creat decreased significantly. After adjustment for confounding variables there was a significant correlation between clinical response and U-CTX II/creat variation. U-CTX II and S-HA at baseline were independently predictive of clinical response. This study showed that 90 days after HA IA injections, U-CTX II levels significantly decrease compared to baseline, suggesting a slowdown of type II collagen degradation.Journal of Orthopaedic Research 10/2011; 30(5):679-85. · 2.81 Impact Factor