Association of serum levels of aggrecan ARGS, NITEGE fragments and radiologic knee osteoarthritis in Tunisian patients.

ABSTRACT

OBJECTIVES: Proteolytic degradation of aggrecan is a hallmark of the pathology of osteoarthritis. The aim of this study was to develop enzyme-linked immunosorbent assay (ELISA) to quantify the serum levels of specific aggrecan fragments generated by aggrecanases-mediated cleavage. We investigated the relationships between these two aggrecan degradations fragments and urinary CTX-II levels. METHODS: The competitive ELISAs employ a polyclonal antibody raised against the aggrecan fragments containing two neoepitopes NITEGE(373)and (374)ARGSVI. We measured serum levels of ARGSV and NITEGE in 125 women with knee osteoarthritis (mean±SD age of 53.6±7.6 years, mean±SD disease duration of 3.6±3.8 years), and 57 women age-matched controls. RESULTS: Aggrecan neoepitopes assays showed an intra- and inter-assay imprecision (CV) lower than 20% for both tests and good linearity. Median serum ARGSVI (by 18%; P=0.002), and NITEGE (36.4%; P<0.001) levels were significantly decreased in patients with knee osteoarthritis compared with controls. Minimal joint space width was negatively correlated with ARGSVI (r=-0.368, P=0.04) and NITEGE (r=-0.274, P=0.038) in knee osteoarthritis patients. Median urinary CTX-II levels were significantly increased by 39.5% (P=0.001) in knee OA patients compared with controls. CONCLUSION: Markers of degradation aggrecan were analyzed for the first time in an African osteoarthritis population. These markers can be used to monitor aggrecanase activity in human joint disease. Their combination with CTX-II can improve clinical investigation of patients with osteoarthritis patients.