Cytokines, metalloproteinases, their inhibitors and cartilage oligomeric matrix protein: relationship to radiological progression and inflammation inearly rheumatoid arthritis. A prospective 5-year study

Objective. To assess how serum concentrations of some cytokines, proteases and their inhibitors and cartilage oligomeric matrix protein (COMP) relate to the evolution of clinical disease and joint damage in early rheumatoid a rthritis (RA). Methods. Annual assessment was performed in 24 RA patients subdivided into thrice groups according to disease severity as determined by the radiologic al progression rate. All patients were followed for 5 yr after inclusion. F unctional status, Larsen's radiographic index in hands and feet (joint dama ge score, JDS) and C-reactive protein (CRP) were assessed annually and comp ared with interleukin (IL)-6, IL-10, the IL-1 receptor antagonist (IL-1Ra), promatrix metalloproteinase 3 (proMMP-3), tissue inhibitor of metalloprote inases 1 (TIMP-1) and COMP. which were determined by specific immunological tests. Results. The median JDS was initially between 4.5 and 7. During the study t ime the progression of JDS was 1 (median) for patients with slow progressio n, 33 for patients with intermediate progression and 62 for patients with r apid progression. Changes in CRP and proMMP-3 concentrations over time diff ered significantly between the groups, but no significant difference was ob served for IL-1Ra, TIMP-1 or COMP. ProMMP-3 was closely related to CRP at e ach time point. IL-6 correlated significantly with CRP at the last four ann ual follow-up examinations. CRP and proMMP-3 correlated with JDS at the las t two or three examinations and the combined levels of these markers over 5 yr correlated significantly with joint damage progression (Spearman rank c orrelation 0.73 and 0.74 respectively). IL-1Ra showed a weak negative corre lation with JDS, and COMP tended to correlate with JDS only at the start. T he initial proMMP-3 concentration was the only significant variable predict ing rapidly developing joint damage, but the predictive value was low. Conclusions. ProMMP-3 correlated closely at all time points with CRP, but g ave little or no additional clinical information regarding inflammation or radiographic progression, IL-1Ra and TIMP-1 showed weaker, acute-phase-like variation, which may reflect pathogenic agonist inhibitor imbalance in the evolution of RA. COMP, in contrast, did not reflect the inflammatory CRP-r elated component of the disease or the destructive aspect in this study.