Abstract
Matrix metalloproteinase-3 (MMP-3) production increases in rheumatoid arthritis (RA) and has been proposed as a marker of disease activity and joint damage. The aim of this cross-sectional study is to examine the usefulness of serum proMMP-3 as an indicator of disease activity and severity in comparison with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Serum proMMP-3 was measured by a quantitative ELISA in 85 RA patients and 70 healthy subjects. Clinical and laboratory measures of disease activity and severity were obtained. Radiological joint damage was assessed by the method of Larsen. Serum proMMP-3 was significantly higher in RA patients than that in the healthy subjects. The active RA patients had significantly higher serum proMMP-3 than the inactive patients. Serum proMMP-3 was significantly correlated with some parameters of disease activity including swollen joints count, proximal interphalangeal joint score, morning stiffness, and Health Assessment Questionnaire; however, ESR and serum CRP were better correlated with all indicators of the disease activity than proMMP-3. The analysis of receiver operating characteristic supported that ESR and CRP had higher performance for reflection of activity compared to proMMP-3. There were no significant associations among Larsen score and proMMP-3, ESR, and CRP. Our results suggest that the cross-sectional measurement of serum proMMP-3 could not give additional information about RA disease activity compared to ESR and CRP, and could not give any information about joint damage.
Similar content being viewed by others
References
Okada Y (2001) Proteinases and matrix degradation. In: Ruddy S, Harris ED, Sledge CB, Budd RC, Sergent JS (eds) Kelly’s textbook of rheumatology. W.B. Saunders, Philadelphia, pp 55–72
Hasty KA, Reife RA, Kang AH, Stuart JM (1990) The role of stromelysin in the cartilage destruction that accompanies inflammatory arthritis. Arthritis Rheum 33:388–397
Nagase H (1997) Activation mechanisms of matrix metalloproteinases. Biol Chem 378:151–160
Manicourt DH, Fujimoto N, Obata K, Thonar EJMA (1995) Levels of circulating collagenase, stromelysin-1, and tissue inhibitor of matrix metalloproteinases 1 in patients with rheumatoid arthritis. Relationship to serum levels of antigenic keratan sulfate and systemic parameters of inflammation. Arthritis Rheum 38:1031–1039
Taylor DJ, Cheung NT, Dawes PT (1994) Increased serum pro-MMP-3 in inflammatory arthritides: a potential indicator of synovial inflammatory monokine activity. Ann Rheum Dis 53:768–772
Yoshihara Y, Obata K, Fujimoto N, Yamashita K, Hayakawa T, Shimmei M (1995) Increased levels of stromelysin-1 in sera from patients with rheumatoid arthritis. Arthritis Rheum 38:969–975
Keyszer G, Lambiri I, Nagel R, Keysser C, Keysser M, Gromnica-Ihle E, Franz J, Burmester GR, Jung K (1999) Circulating levels of matrix metalloproteinases MMP-3 and MMP-1, tissue inhibitor of metalloproteinases 1 (TIMP-1), and MMP-1/TIMP-1 complex in rheumatic disease. Correlation with clinical activity of rheumatoid arthritis versus other surrogate markers. J Rheumatol 26:251–258
Ichikawa Y, Yamada C, Horiki T, Hoshina Y, Uchiyama M (1998) Serum matrix metalloproteinase-3 and fibrin degradation products levels correlate with clinical disease activity in rheumatoid arthritis. Clin Exp Rheumatol 16:533–540
Posthumus MD, Limburg PC, Westra J, van Leeuwen MA, van Rijswijk MH (1999) Serum levels of matrix metalloproteinase-3 in relation to the development of radiological damage in patients with early rheumatoid arthritis. Rheumatology 38:1081–1087
Yamanaka H, Matsuda Y, Tanaka M, Sendo W, Nakajima H, Taniguchi A, Kamatani N (2000) Serum matrix metalloproteinase 3 as a predictor of the degree of joint destruction during the six months after measurement, in patients with early rheumatoid arthritis. Arthritis Rheum 43:852–858
Ribbens C, Martin y Porras M, Franchimont N, Kaiser MJ, Jaspar JM, Damas P, Houssiau FA, Malaise MG (2002) Increased matrix metalloproteinase-3 serum levels in rheumatic diseases: relationship with synovitis and steroid treatment. Ann Rheum Dis 61:161–166
Klimiuk PA, Sierakowski S, Latosiewicz R, Cylwik B, Skowronski J, Chwiecko J (2002) Serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in different histological variants of rheumatoid synovitis. Rheumatology 41:78–87
Sasaki S, Iwata H, Ishiguro N, Obata K, Miura T (1994) Detection of stromelysin in synovial fluid and serum from patients with rheumatoid arthritis and osteoarthritis. Clin Rheumatol 13:228–233
Ribbens C, Andre B, Kaye O, Kaiser MJ, Bonnet V, Jaspar JM, de Groote D, Franchimont N, Malaise MG (2000) Synovial fluid matrix metalloproteinase-3 levels are increased inflammatory arthritides whether erosive or not. Rheumatology 39:1357–1365
Yoshihara Y, Nakamura H, Obata K, Yamada H, Hayakawa T, Fujikawa K, Okada Y (2000) Matrix metalloproteinases and tissue inhibitors of metalloproteinases in synovial fluids from patients with rheumatoid arthritis or osteoarthritis. Ann Rheum Dis 59:455–461
Gravallese EM, Darling JM, Ladd AL, Katz JN, Glimcher LH (1991) In situ hybridization studies of stromelysin and collagenase messenger RNA expression in rheumatoid synovium. Arthritis Rheum 34:1076–1084
Ishiguro N, Ito T, Obata K, Fujimoto N, Iwata H (1996) Determination of stromelysin-1, 72 and 92 kDa type IV collagenase, tissue inhibitor of metalloproteinase-1 (TIMP-1), and TIMP-2 in synovial fluid and serum from patients with rheumatoid arthritis. J Rheumatol 23:1599–1604
Ribbens C, Andre B, Jaspar JM, Kaye O, Kaiser MJ, de Groote D, Malaise MG (2000) Matrix metalloproteinase-3 serum levels are correlated with disease activity and predict clinical response in rheumatoid arthritis. J Rheumatol 27:888–893
Wollheim FA, Eberhardt KB (1992) The search for laboratory measures of outcome in rheumatoid arthritis. Baillieres Clin Rheumatol 6:69–73
van Leeuwen MA, van der Heijde DM, van Rijswijk MH, Houtman PM, van Riel PL, van de Putte LB, Limburg PC (1994) Interrelationship of outcome measures and process variables in early rheumatoid arthritis. A comparison of radiologic damage, physical disability, joint counts, and acute phase reactants. J Rheumatol 21:425–429
So A, Chamot AM, Peclat V, Gerster JC (1999) Serum MMP-3 in rheumatoid arthritis: correlation with systemic inflammation but not with erosive status. Rheumatology (Oxford) 38:407–410
Posthumus MD, Limburg PC, Westra J, van Leeuwen MA, van Rijswijk MH (2000) Serum matrix metalloproteinase 3 in early rheumatoid arthritis is correlated with disease activity and radiological progression. J Rheumatol 27:2761–2768
Cheung NT, Dawes PT, Poulton KV, Ollier WER, Taylor DJ, Mattey DL (2000) High serum levels of pro-matrix metalloproteinase-3 are associated with greater radiographic damage and the presence of the shared epitope in patients with rheumatoid arthritis. J Rheumatol 27:882–887
Cunnane G, Fitzgerald O, Beeton C, Cawston TE, Bresnihan B (2001) Early joint erosions and serum levels of matrix metalloproteinase 1, matrix metalloproteinase 3, and tissue inhibitor of metalloproteinases 1 in rheumatoid arthritis. Arthritis Rheum 44:2263–2274
Posthumus MD, Limburg PC, Westra J, van Leeuwen MA, van Rijswijk MH (2003) Serum matrix metalloproteinase 3 levels in comparison to C-reactive protein in periods with and without progression of radiological damage in patients with early rheumatoid arthritis. Clin Exp Rheumatol 21:465–472
Tchetverikov I, Lard LR, DeGroot J, Verzijl N, TeKoppele JM, Breedveld FC, Huizinga TW, Hanemaaijer R (2003) Matrix metalloproteinases-3, -8, -9 as markers of disease activity and joint damage progression in early rheumatoid arthritis. Ann Rheum Dis 62:1094–1099
Jensen T, Klarlund M, Hansen M, Jensen KE, Skjodt H, Hyldstrup L; Danisit TIRA Group (2004) Connective tissue metabolism in patients with unclassified polyarthritis and early rheumatoid arthritis. Relationship to disease activity, bone mineral density, and radiographic outcome. J Rheumatol 31:1698–1708
Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324
Fries JF, Spitz P, Kraines RG, Holman HR (1980) Measurement of patient outcome in arthritis. Arthritis Rheum 23:137–145
Larsen A, Dale K, Eek M (1977) Radiographic evaluation of rheumatoid arthritis and related conditions by standard reference films. Acta Radiol Diagn 8:481–491
Ritchie DM, Boyle JA, McInnes JM, Jasani MK, Dalakos TG, Grieveson P, Buchanan WW (1968) Clinical studies with an articular index for the assessment of joint tenderness in patients with rheumatoid arthritis. Q J Med 37:393–406
Prevoo MLL, van’t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LBA, van Riel PLCM (1995) Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 38:44–48
Paulus HE, Ramos B, Wong WK, Ahmed A, Bulpitt K, Park G, Sterz M, Clements P (1999) Equivalence of the acute phase reactants C-reactive protein, plasma viscosity, and Westergren erythrocyte sedimentation rate when used to calculate American college of rheumatology 20% improvement criteria or the disease activity score in patients with early rheumatoid arthritis. J Rheumatol 26:2324–2331
Garnero P, Rousseau JC, Delmas PD (2000) Molecular basis and clinical use of biochemical markers of bone, cartilage, and synovium in joint diseases. Arthritis Rheum 43:953–968
Mudgett JS, Hutchinson NI, Chartrain NA, Forsyth AJ, McDonnell J, Singer II, Bayne EK, Flanagan J, Kawka D, Shen CF, Stevens K, Chen H, Trumbauer M, Visco DM (1998) Susceptibility of stromelysin 1-deficient mice to collagen-induced arthritis and cartilage destruction. Arthritis Rheum 41:110–121
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ateş, A., Türkçapar, N., Ölmez, Ü. et al. Serum pro-matrix metalloproteinase-3 as an indicator of disease activity and severity in rheumatoid arthritis: comparison with traditional markers. Rheumatol Int 27, 715–722 (2007). https://doi.org/10.1007/s00296-007-0338-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00296-007-0338-1