Connective tissue metabolites in serum as markers of disease activity in patients with rheumatoid arthritis

The serum levels of aminoterminal type III procollagen peptide (S-PIIINP), immunoreactive prolyl 4-hydroxylase protein (S-IRPH), 7S domain of collagen type IV (S-Col IV, 7S), and fragment P1 of laminin (S-Lam), which are associated with the metabolism of extracellular interstitial collagens and basement membranes, were measured sequentially for two years in 14 rheumatoid arthritis (RA) patients undergoing disease modifying antirheumatic drug treatment. Elevated S-PIIINP, S-IRPH, and S-Col IV, 7S levels were demonstrated in active RA. In active disease the metabolites showed some correlation with clinical and serological signs of disease activity. A high average synovial fluid/serum concentration ratio of PIIINP and of Col IV, 7S supports the concept that the increased serum levels of PIIINP and Col IV, 7S originated from the diseased joints. After 2 years of treatment a decline was observed in S-PIIINP and S-Col IV, 7S in treatment responders. However, the median levels of S-PIIINP and S-IRPH were still above the upper limit of normal, suggesting smouldering, subclinical inflammatory processes. S-Lam remained within the normal range in active and inactive disease.