Serum xylosyltransferase: a new biochemical marker of the sclerotic process in systemic sclerosis

UDP-D-xylose:proteoglycan core protein beta-D-xylosyltransferase (EC 2.4.2. 26) is the initial enzyme in the biosynthesis of chondroitin sulfate and de rmatan sulfate proteoglycans in fibroblasts and chondrocytes. Secretion of xylosyltransferase into the extracellular space was determined in cultured human dermal fibroblasts, A more than 6-fold accumulation of xylosyltransfe rase activity in cell culture supernatant was observed (day 1, 0.6 mu U per 10(6) cells; day 9, 4.1 mu U per 10(6) cells); however, intracellular xylo syltransferase activity remained at a constant level (0.4 mu U per 106 cell s), Exposure of human chondrocytes to colchicine led to a 3-fold decreased level of xylosyltransferase and chondroitin-6-sulfate concentration in cell culture, Specific xylosyltransferase activity and chondroitin-6-sulfate co ncentration decreased in a concentration-dependent manner and in parallel i n culture medium and accumulated 5-fold in cell lysates indicating that xyl osyltransferase is secreted simultaneously into the extracellular space wit h chondroitin sulfate proteoglycans, Xylosyltransferase activities were det ermined in serum samples of 30 patients with systemic sclerosis, Xylosyltra nsferase activities in female (mean value 1.28 mU per liter, 90% range 1.10 -1.55 mU per liter) and male patients (mean 1.39 mU per Liter, 90% range 1. 16-1.57 mU per liter) with systemic sclerosis were significantly increased in comparison with blood donors of a corresponding age, Furthermore, xylosy ltransferase activity was correlated with the clinical classification of sy stemic sclerosis, Female patients with diffuse cutaneous systemic sclerosis showed higher serum xylosyltransferase activities than patients with limit ed systemic sclerosis, These results confirm that the increase of proteogly can biosynthesis in sclerotic processes of scleroderma is closely related t o an elevated xylosyltransferase activity in blood and demonstrate the vali dity of xylosyltransferase as an additional diagnostic marker for determina tion of sclerotic activity in systemic sclerosis.