Y He1, T Manon-Jensen2, L Arendt-Nielsen3, K K Petersen4, T Christiansen5, J Samuels6, S Abramson6, M A Karsdal2, M Attur6, A C Bay-Jensen7. 1. Rheumatology, Biomarkers and Research, Nordic Bioscience, Herlev, Denmark. Electronic address: yhe@nordicbioscience.com. 2. Rheumatology, Biomarkers and Research, Nordic Bioscience, Herlev, Denmark. 3. SMI, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark; C4Pain, Aalborg, Denmark. 4. SMI, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark. 5. Orthopedic Department, Gentofte University Hospital, Hellerup, Denmark. 6. Division of Rheumatology, Department of Medicine, NYU School of Medicine, New York, NY, 10003, USA. 7. Rheumatology, Biomarkers and Research, Nordic Bioscience, Herlev, Denmark. Electronic address: acbj@nordicbioscience.com.
Abstract
OBJECTIVE: Phenotypic changes of chondrocytes toward hypertrophy might be fundamental in the pathogenesis of osteoarthritis (OA), of which type X collagen (Col10) is a well-known marker. The purpose was to develop a specific immunoassay for blood quantification of a newly identified neo-epitope of type Col10 to assess its diagnostic value for radiographic knee OA. METHODS: A neo-epitope of Col10 was identified in urine samples from OA patients. A monoclonal antibody against the neo-epitope was produced in Balb/C mice. The enzyme responsible for the cleavage was identified. Immunohistochemical detection of this neo-epitope was performed on human OA cartilage. An immunoassay (Col10neo) was developed and quantified in two clinical studies: the C4Pain-003 and the NYU OA progression study. Receiver operating characteristic curve (ROC) curve analysis was carried out to evaluate the discriminative power of Col10neo between OA and rheumatoid arthritis (RA). RESULTS: A neo-epitope specific mAb was produced. The Cathepsin K-generated neo-epitope was localized to the pericellular matrix of chondrocytes, while its presence was extended and more prominent in superficial fibrillation in the cartilage with advanced degradation. In the C4Pain study, a higher level of Col10neo was seen in subjects with greater KL grade. The group of the highest tertile of Col10neo included more subjects with KL3-4. In the NYU study, Col10neo was statistically higher in OA than control or RA. ROC curve analysis revealed area under the curve was 0.88 (95% CI 0.81-0.94). CONCLUSION: Our findings indicate that Col10neo linked to hypertrophic chondrocytes could be used as a diagnostic biochemical marker for knee OA.
OBJECTIVE: Phenotypic changes of chondrocytes toward hypertrophy might be fundamental in the pathogenesis of osteoarthritis (OA), of which type X collagen (Col10) is a well-known marker. The purpose was to develop a specific immunoassay for blood quantification of a newly identified neo-epitope of type Col10 to assess its diagnostic value for radiographic knee OA. METHODS: A neo-epitope of Col10 was identified in urine samples from OA patients. A monoclonal antibody against the neo-epitope was produced in Balb/C mice. The enzyme responsible for the cleavage was identified. Immunohistochemical detection of this neo-epitope was performed on human OA cartilage. An immunoassay (Col10neo) was developed and quantified in two clinical studies: the C4Pain-003 and the NYU OA progression study. Receiver operating characteristic curve (ROC) curve analysis was carried out to evaluate the discriminative power of Col10neo between OA and rheumatoid arthritis (RA). RESULTS: A neo-epitope specific mAb was produced. The Cathepsin K-generated neo-epitope was localized to the pericellular matrix of chondrocytes, while its presence was extended and more prominent in superficial fibrillation in the cartilage with advanced degradation. In the C4Pain study, a higher level of Col10neo was seen in subjects with greater KL grade. The group of the highest tertile of Col10neo included more subjects with KL3-4. In the NYU study, Col10neo was statistically higher in OA than control or RA. ROC curve analysis revealed area under the curve was 0.88 (95% CI 0.81-0.94). CONCLUSION: Our findings indicate that Col10neo linked to hypertrophic chondrocytes could be used as a diagnostic biochemical marker for knee OA.
Authors: Christian S Thudium; Signe Holm Nielsen; Samra Sardar; Ali Mobasheri; Willem Evert van Spil; Rik Lories; Kim Henriksen; Anne-Christine Bay-Jensen; Morten A Karsdal Journal: BMC Musculoskelet Disord Date: 2020-11-28 Impact factor: 2.362