Levels of serum matrix metalloproteinase-3 correlate with disease activity in the enthesitis-related arthritis category of juvenile idiopathic arthritis

Abstract

Objective. Serum matrix metalloproteinase-3 (MMP-3) has been shown to reflect disease activity in ankylosing spondylitis (AS) and rheumatoid arthritis. Elevated levels have been found in juvenile idiopathic arthritis (JIA). In the enthesitis-related arthritis category of JIA (JIA-ERA), we studied whether serum MMP-3 levels and ratios of MMP-3/tissue inhibitor of metalloproteinase (TIMP-1) are correlated with disease activity and whether they are sensitive to change in disease activity. Methods. A total of 54 patients with JIA-ERA (International League of Associations for Rheumatology criteria) were enrolled for study. Baseline disease activity measures included tender and swollen joint counts, Maastricht AS Enthesitis Score, Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), patient assessment of pain and global disease activity, physician assessment of global disease activity, and erythrocyte sedimentation rate (ESR). Serum MMP-3 and TIMP-1 levels were measured using ELISA. A group of 24 patients were followed up for longitudinal study. Results. The mean age of 54 patients (48 males) at disease onset was 11.8 ± 4.19 years and duration of disease was 5.2 ± 4.3 years. Median ESR was 65 mm/h (range 46.5–97) and median BASDAI was 3.4 (range 2.5–4.7). Median MMP-3, TIMP-1, and MMP-3/TIMP-1 ratio were 50.4 ng/ml (IQR 13.0–193.8), 228.9 ng/ml (IQR 108.2–290.4), and 0.3 (IQR 0.07–1.13), respectively. At inclusion MMP-3 levels correlated directly with various disease activity measures: tender joint count (TJC; r = 0.60), swollen joint count (SJC; r = 0.45), BASFI (r = 0.29), BASDAI (r = 0.32), ESR (r = 0.49), physician global assessment (r = 0.40), patient visual analog scale for pain (r = 0.28), and patient global assessment (r = 0.38; all p < 0.05). MMP-3/TIMP-1 ratio correlated only with TJC (r = 0.51), SJC (r = 0.39), and ESR (r = 0.34; p < 0.05). At followup, change in MMP-3 correlated with changes in TJC (r = 0.42) and SJC (r = 0.44; p < 0.05), while change in ESR did not correlate with change in any disease activity measure. Conclusion. MMP-3 levels are a good marker for disease activity in JIA-ERA.