SEROMARKERS OF COLLAGEN-I AND COLLAGEN-III METABOLISM IN ACTIVE CROHNS-DISEASE - RELATION TO DISEASE-ACTIVITY AND RESPONSE TO THERAPY

Crohn's disease is characterised by gradual development of intestinal fibrotic lesions containing large amounts of collagen type I, III, and V. Measurement of circulating connective tissue metabolites has emerged as a useful tool for assessment of fibroproliferative activity in various diseases. Serum concentrations of procollagen peptides, N-terminal propeptide of type III procollagen (PII-INP), and C-terminal propeptide of type I procollagen (PICP), reflect the synthesis rate of the parent collagens, while the C-terminal telopeptide of type I collagen (ICTP) reflects its degradation. S-PIIINP, S-PICP, and S-ICTP were measured by radioimmunoassays in 29 patients with active Crohn's disease. S-ICTP was significantly increased, median 6.2 mu g/l (95% CI 5.2 to 8.7 mu g/l) versus controls 2.6 mu g/l (2.5 to 2.7 mu g/l) (p < 0.0001), S-PICP reduced, 100 mu g/l (80 to 110 mu g/l) versus 132 mu g/l (124 to 141 mu g/l) (p=0.001), and S-PIIINP did not differ from controls. Patients with sustained clinical remission during prednisolone therapy exhibited an increase in S-PICP (p=0.0052). S-PIIINP changed significantly (p=0.0002), however, exhibiting a biphasic pattern. S-ICTP decreased (p=0.015) in treatment responders but remained above the upper normal limit even when clinical remission had been achieved. Nonresponders showed no significant changes in any of the marker molecules of collagen synthesis or degradation. Correlations were found between S-ICTP and S-PICP (p<0.005) and S-ICTP (p<0.02), and between S-ICTP and S-orosomucoid (p<0.005) and S-C reactive protein (p<0.02). By contrast, there was no relation between the connective tissue metabolites and Harvey Bradshaw Index. These data provide evidence that collagen I degradation is increased not only in active Crohn's disease, but also in patients entering clinical remission. The concurrent normal/low-normal values of markers of collagen formation may reflect a changed local or systemic elimination of the propeptides.