Serum MMP-3 and MMP-1 and progression of joint damage in early rheumatoid arthritis

Rheumatology (Oxford). 2003 Jan;42(1):83-8. doi: 10.1093/rheumatology/keg037.


Objective: Expression and activation of matrix metalloproteinases such as MMP-3 (stromelysin-1) and MMP-1 (collagenase-1) are increased in patients with rheumatoid arthritis (RA). Previous negative reports of their value as predictors of joint damage may be due to the lack of a large longitudinal study of early RA patients. This study evaluated their use in assessing early untreated patients with RA and predicting subsequent joint damage.

Methods: Ninety-eight patients with early untreated RA of less than 12 months duration and 20 normal controls had baseline serum samples tested with a double-antibody enzyme-linked immunosorbent assay for each of MMP-1 and MMP-3. The subsequent changes in Larsen score (DeltaLarsen) and Health Assessment Questionnaire (DeltaHAQ) over the first 12 months were recorded.

Results: Baseline serum levels of MMP-3 and MMP-1 correlated significantly with baseline C-reactive protein (CRP) (r=0.42 and 0.49, P<0.001), DeltaHAQ (r=0.32 and 0.30, P<0.01) and DeltaLarsen (r=0.23 and 0.32, P<0.05) respectively. Analysis of the group of patients with a normal CRP at presentation (n=21) showed correlation of the baseline MMP-3 and MMP-1 with the presence of erosive disease during the first 12 months (r=0.52 and 0.65 respectively, P<0.05). Logistic regression analysis, in the patients who were non-erosive at presentation, showed that the strongest correlation with progression in Larsen score was the baseline MMP-3 level (r=0.30, P=0.01).

Conclusions: Baseline serum MMP-1 and MMP-3 levels correlate with disease activity and predict functional and radiographic outcome in early untreated RA. They may have a particular value in predicting the progression of erosive disease in patients who are not erosive at presentation.

MeSH terms

  • Arthritis, Rheumatoid / enzymology*
  • Arthritis, Rheumatoid / pathology
  • Biomarkers / blood
  • C-Reactive Protein / analysis
  • Case-Control Studies
  • Disease Progression
  • Enzyme Activation
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Humans
  • Joints / pathology*
  • Logistic Models
  • Male
  • Matrix Metalloproteinase 1 / blood*
  • Matrix Metalloproteinase 3 / blood*
  • Middle Aged
  • Prognosis


  • Biomarkers
  • C-Reactive Protein
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 1