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 emerg ed as a useful tool for assessment of fibroproliferative activity in v arious diseases. Serum concentrations of procollagen peptides, N-termi nal propeptide of type III procollagen (PII-INP), and C-terminal prope ptide 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 mea sured 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 (12 4 to 141 mu g/l) (p=0.001), and S-PIIINP did not differ from controls. Patients with sustained clinical remission during prednisolone therap y exhibited an increase in S-PICP (p=0.0052). S-PIIINP changed signifi cantly (p=0.0002), however, exhibiting a biphasic pattern. S-ICTP decr eased (p=0.015) in treatment responders but remained above the upper n ormal limit even when clinical remission had been achieved. Nonrespond ers showed no significant changes in any of the marker molecules of co llagen synthesis or degradation. Correlations were found between S-ICT P and S-PICP (p<0.005) and S-ICTP (p<0.02), and between S-ICTP and S-o rosomucoid (p<0.005) and S-C reactive protein (p<0.02). By contrast, t here was no relation between the connective tissue metabolites and Har vey Bradshaw Index. These data provide evidence that collagen I degrad ation is increased not only in active Crohn's disease, but also in pat ients entering clinical remission. The concurrent normal/low-normal va lues of markers of collagen formation may reflect a changed local or s ystemic elimination of the propeptides.