Background Cartilage degradation and inflammation of synovial and connective tissue are key events in inflammatory and non-inflammaory arthropathies, such as osteoarthritis (OA), rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Presently there are no prognostic tools available for measuring these tissue related processes, which are often the target of intervention. Inflammation induces an increase in collagenases. An elevated level of collagenases will lead to increased degradation of the disease affected tissues, e.g. cartilage and synovial tissue. Type II collagen is the primary protein component of cartilage and type III collagen is one of the major proteins of many connective tissues (e.g. synovial membrane); thus they are obvious targets for the action of collagenases.
Objectives The objective of the study was to investigate the diagnostic utility of cartilage and synovial turnover biomarkers is RA and AS. Furthermore to investigate the prognostic utility of those biomarkers in relation to radiographic disease progression in AS.
Methods erum samples from RA patients (n=47) were retrieved from patients prior to the start of treatment with biologics. Patients are eligible for biologics in the Province of Alberta if they have active disease despite treatment with methotrexate, a methotrexate combination with a second disease modifying agent, and leflunomide.Serum samples were collected from patient suffering from AS (n=124) at baseline and 2-3 month treatment follow-up. Standard AS clinical outcome scores were collected: BASDAI (health questionnaire) and mSASSS (radiographic scoring). Progressors were defined as having new vertebra syndesmophytes over a two year period. SSerum levels of type II collagen degradation was measured by the C2M competitive ELISA, and type III collagen degradation by the C3M ELISA. Serum hsCRP was likewise measured. Logistic regression and CART were used to analyze the prognostic value of the markers individually or in combination.
Results Both serum C2M and C3M were significantly elevated in RA patients compared to controls, P<0.0001. Diagnostic utility was analyzed by ROC and the AUCs were 72% and 89% for C2M and C3M, respectively.Both cartilage and connective tissue degradation fragments, C2M and C3M, were significantly elevated in serum samples from AS patient compared to healthy controls (p<0.0001). The area under the curves of C2M and C3M, respectively, were 70% and 81% for AS. C3M correlated significantly with AS score BASDAI and mSASSS (p<0.01). C2M did not show the same correlations. A combination of the two markers could identify 80% of those who was defined as progressors, 61% of the non-progressors.
Conclusions Present study is the first to show that the two novel biomarkers of cartilage and synovial tissue degradation add additional information to the understanding of the diagnosis and progression of rheumatic diseases. No other serum biomarker possesses these properties.
Disclosure of Interest None Declared
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