Elsevier

Joint Bone Spine

Volume 75, Issue 5, October 2008, Pages 559-562
Joint Bone Spine

Original article
Serum levels of MMP-3 and cathepsin K in patients with ankylosing spondylitis: Effect of TNFα antagonist therapy

https://doi.org/10.1016/j.jbspin.2008.01.026Get rights and content

Abstract

Objective

To measure serum levels of MMP-3 and cathepsin K in patients with ankylosing spondylitis (AS) and in controls and to look for changes in these variables during TNFα antagonist therapy.

Methods

We prospectively studied a group of patients who met New York criteria for AS and a group of healthy volunteers. We recorded age, disease duration, main features of the disease, BASDAI, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Serum MMP-3 and cathepsin K were assayed in duplicate using ELISA kits (Quantikine MMP-3, R&D Systems; and Cathepsin K, Biomedica). We also assayed IL-17 (Quantikine IL-17, R&D Systems) and BMP-7 (human BMP-7 DuoSet, R&D Systems). In patients treated with TNFα antagonists, the assays were repeated 10 weeks after treatment initiation. The Mann–Whitney test was used for between-group comparisons and the Wilcoxon test for evaluations of changes under treatment. Correlation testing was performed. P-values less than 0.05 were considered significant.

Results

We studied 23 outpatients with AS and 21 controls, with mean age of 39.9 years and 41.2 years, respectively (NS). Disease duration was 10.1 years (1.3); most patients had axial disease (n = 21) and carried HLA-B27 (n = 19). At baseline, the mean BASDAI was 44.1 mm (4.1) and the mean CRP level was 22.3 mg/L (4.7). Serum MMP-3 levels were significantly higher in the patients than in the controls (4.71 vs. 2.79 ng/ml, P = 0.04); levels were also higher for cathepsin K (6.4 vs. 3.6 pg/ml) and IL-17 (60.4 vs. 32 pg/ml), but the differences were not statistically significant. No difference was noted for BMP-7. The only positive correlation was between the ESR and the CRP level (P = 0.0002). Thirteen patients were evaluated 10 weeks into TNFα antagonist therapy (adalimumab, n = 7; etanercept, n = 4; or infliximab, n = 2). Serum MMP-3 decreased significantly (P = 0.04); significant decreases were also noted for the ESR, CRP, and BASDAI.

Conclusion

MMP-3 is significantly increased in patients with active AS but fails to correlate significantly with conventional variables used to assess disease activity. TNFα antagonist therapy induces a significant decrease in MMP-3 levels, together with decreases in conventional variables (ESR, CRP, and BASDAI). MMP-3 may be a biomarker for disease activity in AS but supplies no additional information to the clinician.

Section snippets

Methods

We prospectively included outpatients who met modified New York criteria for AS [11]. For each patient, we recorded age, disease duration, main features, and treatment. To assess disease activity, we used the validated French version of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) [12] and we measured the erythrocyte sedimentation rate (ESR) and the serum C-reactive protein level (CRP). The control group was composed of healthy volunteers who had no known diseases and were

Results

We included 23 patients with AS and 21 age-matched healthy controls. The patients were 18 men and 5 women with a mean disease duration of 10.1 ± 1.3 years and predominant involvement of the axial skeleton (21/23 patients). Most of the patients (19/23, 82%) were HLA-B27-positive. The BASDAI was 44.1 ± 4.1, CRP was 22.3 ± 4.7 mg/L, and ESR was 27.8 ± 5.3 mm/h. None of the patients were taking glucocorticoids or immunomodulating drugs. Nonmusculoskeletal manifestations included inflammatory bowel disease in

Discussion

In a group of patients with active AS (BASDAI > 40) chiefly involving the axial skeleton, serum MMP-3 levels were significantly elevated compared to healthy controls. None of our patients was taking immunosuppressive drugs or glucocorticoids, which may increase MMP-3 levels [13]. Similarly, in 17 patients with axial AS and 16 with axial and appendicular AS, serum MMP-3 levels were elevated compared to healthy controls [14]. MMP-3 production indicated the presence of peripheral synovitis: MMP-3

References (17)

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This study was funded by the Association Franc-Comtoise pour la Formation, la Recherche et l'Enseignement en Rhumatologie.

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