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Serum Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Patients with Early Rheumatoid Arthritis
MALGORZATA FIEDORCZYK, PIOTR ADRIAN KLIMIUK, STANISLAW SIERAKOWSKI, EWA GINDZIENSKA-SIESKIEWICZ, and JUSTYNA CHWIECKO ABSTRACT. Objective. To analyze serum concentrations of matrix metalloproteinases (MMP) MMP-1, MMP-3, MMP-9, MMP-13, tissue inhibitors of MMP (TIMP) TIMP-1 and TIMP-2, and MMP/TIMP ratios in patients with early rheumatoid arthritis (RA) before and after 6 months of treatment with methotrexate (MTX). Methods. The study group consisted of 30 patients with RA, not treated with disease modifying antirheumatic drugs or corticosteroids, with disease duration < 3 years. Twenty patients with osteoarthritis (OA) served as a control group. Analysis of serum concentrations of MMP and TIMP was based on a quantitative sandwich ELISA. Results. Serum concentrations of MMP-1, MMP-3, MMP-9, and MMP-13 were higher in untreated patients with early RA than in OA patients (p < 0.001 in all cases). Serum levels of TIMP-1 and TIMP-2 dominated in the serum of RA patients compared with controls (p < 0.01 and p < 0.05, respectively). Ratios of MMP to TIMP were significantly higher in patients with early RA versus controls. Six months' treatment with MTX downregulated serum concentrations of MMP-1 (p < 0.001), MMP-3 (p < 0.001), MMP-9 (p < 0.001), MMP-13 (p < 0.01), and TIMP-1 (p < 0.05) in patients with RA. These changes were accompanied by significantly reduced ratios of MMP to TIMP. MTX treatment decreased markers of RA activity such as the number of painful and swollen joints, erythrocyte sedimentation rate, Disease Activity Score, and C-reactive protein. Conclusion. Patients with early RA are characterized by high serum concentrations of tissue-degrading metalloproteinases. Therapy with MTX resulted in clinical improvement and reduced serum MMP levels in patients with RA, confirming effectiveness of MTX in patients in early stages of the disease. (J Rheumatol 2006;33:1523–9) Key Indexing Terms:
MATRIX METALLOPROTEINASES From the Department of Rheumatology and Internal Diseases, Medical University of Bialystok, Bialystok, Poland. M. Fiedorczyk, MD, PhD, Assistant; P.A. Klimiuk, MD, PhD, Assistant; S. Sierakowski, MD, PhD, DSc (Med), Professor and Chairman; E. Gindzienska-Sieskiewicz, MD, PhD, Assistant; J. Chwiecko, MA, PhD, Principal Technician. Address reprint requests to Dr. P.A. Klimiuk, Department of Rheumatology and Internal Diseases, Medical University of Bialystok, M.C. Sklodowskiej 24a, 15-276 Bialystok, Poland. E-mail: klimp@amb.edu.pl Accepted for publication March 16, 2006.
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