Circulating type I collagen degradation products: a new serum marker for clinical severity in patients with scleroderma?

Systemic sclerosis (SSc; scleroderma) results in the excessive deposition o f extracellular matrix components in affected organs. This is partly due to enhanced synthesis; however, the role of degradative processes in this dis ease is still poorly understood. Sera of 32 patients with SSc (72 with the diffuse, 10 with the limited form) and of six patients with morphoea were a ssessed using radioimmunoassays for the cross-linked carboxy terminal telop eptide of type I collagen (ICTP) and for the amino terminal propeptide of t ype I procollagen (PINP) reflecting type I collagen degradation and synthes is, respectively. In 27 of the 32 patients with SSc, the concentration of I CTP was above the upper limit of the normal value (4.6 mu g/L) and the mean level was clearly elevated at 7.92 mu g/L. The ICTP concentration correlat ed with the skin score measuring the ex-tent of the lesions, whereas no suc h correlation was found for PINP, The ICTP antigen in serum, studied by imm unoblotting, had a molecular weight of about twice that of the trypsin-gene rated fragment isolated from human bone collagen. The mean concentration of serum PINP was 43.9 mu g/L and no patient exceeded the upper limit of the normal range (80 mu g/L). We report here for the first time that the concen tration of the type I collagen degradation product ICTP in serum shows a cl ose correlation with the extent of skin fibrosis in patients with SSc. We c onclude that the increased deposition of type I collagen in this disease is accompanied by an increased turnover of this molecule, indicating a more c omplex derangement of synthetic and degradative processes than previously a cknowledged.