A NEW BIOCHEMICAL MARKER FOR JOINT INJURY. ANALYSIS OF YKL-40 IN SERUM AND SYNOVIAL FLUID

Abstract

We report the development of the first radiomimunoassay for YKL–40, a M, = 40 kDa protein which is secreted at high levels by human synovial cells and articular cartilage chondrocytes, and by the human osteosarcoma cell line MG63. This assay uses YKL–40 purilied from the conditioned medium of MG63 cells as standard and tracer, and as antigen for immunizing rabbits. With this assay we have discovered high levels of YKL–40 antigen in serum and SF. The molecular weight of serum and SF YKL–40 is identical to purified YKL–40. To evaluate the possible utility of YKL–40 in the assessment of joint disease, we measured YKL-40 in serum and SF of 49 patients with various forms of inflammatory and degenerative joint disease and in the serum of 50 normal adults. The YKL level in serum was significantly higher (P<0.001) in the patients compared to the normal adults, but there was no difference in serum YKL–40 between the patients with inflammatory joint diseases and OA. The SF levels of YKL–40 were 15–fold higher than serum levels and there was a significant correlation (r = 0.55, P<0.001) between YKL–40 concentration in SF and serum. Although the tissue distribution of YKL–40 secretion is presently unknown, these observations suggest that a major portion of serum YKL–40 in fact arises from the joint. Serum and SF YKL–44) levels correlated significantly (P<0.05–Pc0.001) with other indices of joint disease: serum CRP, SF IL–6, and the elastolytic activity of monocytes/macrophages in SF. Serum YKL–40 also correlated with serum PIIINP and elastolytic activity of blood monocytes/macrophages. These studies indicate that serum and SF YKL–40 levels reflect joint disease and a YKL–40 determination may therefore be useful in the evaluation of connective tissue injury and repair in patients with inflammatory or degenerative rheumatic diseases. Future studies will be needed in order to assess the physiologic significance of elevated YKL–40 levels in patients with rheumatoid diseases.