NOVEL MARKER FOR RHEUMATOID ARTHRITIS DISEASE ACTIVITY

Abstract

RATIONALE: Rheumatoid arthritis (RA) is a chronic autoimmune disease, characterized by pain in affected joints, stiffness, and symmetrical synovitis. Synovial membrane inflammation of diarthrodial joints is a distinctive feature of RA, leading to articular damage, decline in motility and eventually complications, such as cardiomyopathy, neurologic and metabolic disorders. Currently available biomarkers are not satisfactory in terms of monitoring disease activity of RA. AIM: The objective of this study is to show Collagen triple helix repeat containing 1 (CTHRC1) protein`s potential in monitoring RA disease activity HYPOTHESIS: CTHRC1 is a potential biomarker for assessing RA disease activity. The diagnosis of RA depends primarily on clinical assessments. Serology tests routinely used in RA diagnosis are Anti-citrullinated peptide antibody (ACPA) and Rheumatoid factor (RF) level determination in serum/plasma. However, the value of RF for assessing RA remains debatable, because it is also detected in connective tissue diseases, chronic infections, malignancy and in healthy individuals. In comparison, ACPA’s are present in the peripheral blood of almost 80% of RA patients with higher diagnostic specificity. However, in our study ACPA was not associated with disease activity in patients with established diagnosis of RA. Demand for quantitative assessment of disease activity in RA for the improvement of disease diagnosis, prognosis and management is still high. Here I had proposed that the CTHRC1 is a marker of differential diagnosis of RA from OA, ReA and showed high potential to be used to monitor disease activity. METHODS: For this clinical cross sectional study in total 148 individuals with established diagnosis of RA (57), Osteoarthritis (OA-65), Reactive arthritis (ReA-12) and healthy volunteers (14) were recruited. All patients were undergoing treatment at the time of enrollment. Prior collecting and testing plasma samples of patients, they were clinically assessed, including current status, number of swollen and tender joints, tested for complete blood count parameters, current level of RF and ACPA, and also MRI and X-ray of knee joints were performed. Collected plasma samples were tested for the levels of CTHRC1, pro-inflammatory cytokines, such as interleukin 1 beta (IL-1b), interleukin 6 (IL-6), interleukin 8 (IL-8), and interferon gamma (IFN g). All collected data were analyzed including comparison among groups, correlation within each group and Receiver operating characteristic (ROC) analysis was further performed to assess the diagnostic value of CTHRC1. CONCLUSION: This study showed high levels of CTHRC1 protein in RA plasma. These results indicate that CTHRC1 can be used as a novel plasma biomarker to evaluate disease activity in RA. Also it can be used for the differential diagnosis of RA from similar joint diseases, such as OA and ReA.