A Robin Poole1, Nhuan Ha1, Suzanne Bourdon1, Eric C Sayre1, Ali Guermazi1, Jolanda Cibere2. 1. From the Division of Orthopedics, Department of Surgery, Faculty of Medicine, McGill University, Montreal, Quebec; R&D Diagnostics, IBEX Pharmaceuticals, Montreal, Quebec; Arthritis Research Canada, Richmond, British Columbia, Canada; Department of Radiology, Boston University School of Medicine, Boston, Massachusetts, USA; Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.A.R. Poole, PhD, DSc, Professor Emeritus, Division of Orthopedics, Department of Surgery, Faculty of Medicine, McGill University; N. Ha, PhD, Manager, R&D Diagnostics, IBEX Pharmaceuticals, currently affiliated with Beckman Coulter, Miami, Florida, USA; S. Bourdon, BSc, Manager, Assay Production, IBEX Pharmaceuticals; E.C. Sayre, PhD, Statistical Analyst, Arthritis Research Canada; A. Guermazi, MD, PhD, Professor, Department of Radiology, Boston University School of Medicine; J. Cibere, MD, PhD, Associate Professor, Department of Medicine, University of British Columbia, and Senior Scientist, Arthritis Research Canada. 2. From the Division of Orthopedics, Department of Surgery, Faculty of Medicine, McGill University, Montreal, Quebec; R&D Diagnostics, IBEX Pharmaceuticals, Montreal, Quebec; Arthritis Research Canada, Richmond, British Columbia, Canada; Department of Radiology, Boston University School of Medicine, Boston, Massachusetts, USA; Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.A.R. Poole, PhD, DSc, Professor Emeritus, Division of Orthopedics, Department of Surgery, Faculty of Medicine, McGill University; N. Ha, PhD, Manager, R&D Diagnostics, IBEX Pharmaceuticals, currently affiliated with Beckman Coulter, Miami, Florida, USA; S. Bourdon, BSc, Manager, Assay Production, IBEX Pharmaceuticals; E.C. Sayre, PhD, Statistical Analyst, Arthritis Research Canada; A. Guermazi, MD, PhD, Professor, Department of Radiology, Boston University School of Medicine; J. Cibere, MD, PhD, Associate Professor, Department of Medicine, University of British Columbia, and Senior Scientist, Arthritis Research Canada. jcibere@arthritisresearch.ca.
Abstract
OBJECTIVE: To evaluate the association of a sandwich assay for cartilage collagenase-mediated degradation, the C2C human urine sandwich assay (IB-C2C-HUSA), with early and late knee cartilage pathology and with progression of cartilage damage. METHODS: A population-based cohort with knee pain, age 40-79 years, was evaluated at baseline (n = 253) and after mean 3.3 years (n = 161). We evaluated the IB-C2C-HUSA and a related competitive inhibition assay (C2C). The C2C assay was applied to serum (sC2C) and urine (uC2C). Based on knee radiographs and magnetic resonance imaging (MRI), 3 subgroups [no cartilage pathology, preradiographic cartilage pathology, and radiographic osteoarthritis (ROA)] were evaluated cross-sectionally for association with biomarker levels. Longitudinally, we evaluated whether baseline assays predict subsequent progression of cartilage degeneration, defined by MRI cartilage loss. RESULTS: Cross-sectionally, statistically significant differences were seen in the 3 subgroups for IB-C2C-HUSA (p < 0.001), with the highest levels seen in ROA, and for sC2C (p = 0.023), while no differences were seen for uC2C (p = 0.501). Baseline IB-C2C-HUSA levels were higher in progressors vs nonprogressors (p = 0.003). In logistic regression analysis, only baseline IB-C2C-HUSA was associated with an increased risk of progression of cartilage damage (OR 1.78, 95% CI 1.03-3.09). CONCLUSION: The IB-C2C-HUSA degradation assay detects the generation of a pathology-related cartilage collagen peptide(s) that increase(s) with onset of degeneration of knee articular cartilage. The baseline values are associated with progression of cartilage degeneration over 3 subsequent years. This assay may have value in clinical OA trials. Further, it points to collagenase activity as a therapeutic target for controlling degeneration of articular cartilage.
OBJECTIVE: To evaluate the association of a sandwich assay for cartilage collagenase-mediated degradation, the C2C human urine sandwich assay (IB-C2C-HUSA), with early and late knee cartilage pathology and with progression of cartilage damage. METHODS: A population-based cohort with knee pain, age 40-79 years, was evaluated at baseline (n = 253) and after mean 3.3 years (n = 161). We evaluated the IB-C2C-HUSA and a related competitive inhibition assay (C2C). The C2C assay was applied to serum (sC2C) and urine (uC2C). Based on knee radiographs and magnetic resonance imaging (MRI), 3 subgroups [no cartilage pathology, preradiographic cartilage pathology, and radiographic osteoarthritis (ROA)] were evaluated cross-sectionally for association with biomarker levels. Longitudinally, we evaluated whether baseline assays predict subsequent progression of cartilage degeneration, defined by MRI cartilage loss. RESULTS: Cross-sectionally, statistically significant differences were seen in the 3 subgroups for IB-C2C-HUSA (p < 0.001), with the highest levels seen in ROA, and for sC2C (p = 0.023), while no differences were seen for uC2C (p = 0.501). Baseline IB-C2C-HUSA levels were higher in progressors vs nonprogressors (p = 0.003). In logistic regression analysis, only baseline IB-C2C-HUSA was associated with an increased risk of progression of cartilage damage (OR 1.78, 95% CI 1.03-3.09). CONCLUSION: The IB-C2C-HUSA degradation assay detects the generation of a pathology-related cartilage collagen peptide(s) that increase(s) with onset of degeneration of knee articular cartilage. The baseline values are associated with progression of cartilage degeneration over 3 subsequent years. This assay may have value in clinical OA trials. Further, it points to collagenase activity as a therapeutic target for controlling degeneration of articular cartilage.
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Keywords:
IMMUNOASSAY; OSTEOARTHRITIS; TYPE II COLLAGEN
Authors: Anne C Bay-Jensen; Ali Mobasheri; Christian S Thudium; Virginia B Kraus; Morten A Karsdal Journal: Curr Opin Rheumatol Date: 2022-01-01 Impact factor: 5.006
Authors: Heide Boeth; Peter C Raffalt; Aoife MacMahon; A Robin Poole; Felix Eckstein; Wolfgang Wirth; Frank Buttgereit; Patrik Önnerfjord; Pilar Lorenzo; Cecilia Klint; Anna Pramhed; Georg N Duda Journal: J Exp Orthop Date: 2019-05-03