Serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in ankylosing spondylitis: MMP-3 is a reproducibly sensitive and specific biomarker of disease activity

Abstract

To submit serum levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) to statistical analyses to test their exact degrees of clinical usefulness as biomarkers for detecting high disease activity in ankylosing spondylitis (AS), comparing them with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Serum levels of MMP-1, -3, -9 and TIMP-1 and -2 were measured in 42 AS patients and 20 healthy controls. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) provided the gold standard for measuring disease activity. Patients with BASDAI > or =4 were regarded as having high disease activity. The results were compared with results for a separate cohort of 41 AS patients. Only MMP-3 levels were significantly higher in AS patients than in healthy controls (P<0.001). Within AS patients, MMP-3 levels were also higher in patients with high disease activity compared with those with low disease activity, and correlated significantly with BASDAI (r = 0.366, P = 0.017) and functional indices (r = 0.344, P = 0.026). The correlation with BASDAI was stable in a 1-yr follow-up (r = 0.464, P = 0.095) and reproducible with two different enzyme-linked immunosorbent assays. For detecting high disease activity, the sensitivity and specificity of MMP-3 level was 69.2 and 68.8% respectively. Most importantly, using receiver operating characteristic plots to analyse the two cohorts, MMP-3 was more accurate than ESR and CRP in detecting AS patients with high disease activity (P = 0.01 and P = 0.009, respectively). Using several analytical approaches that have never been reported previously, we showed that MMP-3 is a more useful biomarker than ESR and CRP to detect high disease activity in AS.