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Serum matrix metalloproteinase-9 levels as a diagnostic or as a prognostic marker of disease.
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Jose E. Tanus-Santos, Assistant Professor Faculty of Medicine of Ribeirao Preto - University of Sao Paulo, Raquel F. Gerlach
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tanus{at}fmrp.usp.br Jose E. Tanus-Santos, et al.
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Dear Editor, Ko et al. have recently compared matrix metalloproteinase (MMP)-9 activity and tissue inhibitor of metalloproteinase (TIMP)-1 expression in the serum and bronchoalveolar lavage fluid (BALF) in healthy subjects, patients with mild/moderate asthma, patients with severe asthma, and patients with asthmatic mucus hypersecretion (AMH)1. They have also compared MMP-9 activity in serum and BALF. Their basic hypothesis was that MMP-9 activity would be increased in the serum and airway secretions in asthmatic patients who had severe disease and/or AMH. While they have found high MMP -9 levels in the BALF of patients who had AMH or severe asthma, no correlation was reported between the levels of MMP-9 or TIMP-1 between serum and BALF1. We believe that their results are of great clinical significance, however, there is evidence indicating that their MMP-9 results in serum do not reliably reflect the circulating levels of MMP-9 and may explain the lack of correlation between the circulating levels of MMP-9 and the levels of MMP-9 in the BALF. Measurement of MMP-9 levels in serum have been reported as artificially high compared with the results obtained from plasma samples2-5. In addition, there is no correlation between MMP-9 levels in serum and in plasma. In summary, preanalytical conditions and other methodological issues are of major importance when assessing MMPs in clinical samples6. Therefore, we believe that serum samples should not be used to assess circulating matrix metalloproteinase- 9 levels as a diagnostic or as a prognostic marker of disease7. References 1.Ko FW, Diba C, Roth M, et al. A comparison of airway and serum matrix metalloproteinase-9 activity among normal subjects, asthmatic patients, and patients with asthmatic mucus hypersecretion. Chest. 2005;127:1919-1927. 2.Jung K, Lein M, Laube C, et al. Blood specimen collection methods influence the concentration and the diagnostic validity of matrix metalloproteinase 9 in blood. Clin Chim Acta. 2001;314:241-244. 3.Jung K, Laube C, Lein M, et al. Kind of sample as preanalytical determinant of matrix metalloproteinase 2 and 9 and tissue inhibitor of metalloproteinase 2 in blood. Clin Chem. 1998;44:1060-1062. 4.Gerlach RF, Uzuelli JA, Souza-Tarla CD, et al. Effect of anticoagulants on plasma matrix metalloproteinase (MMP)-2 and MMP-9 activities. Anal Biochem. 2005;in Press 5.Makowski GS, Ramsby ML. Use of citrate to minimize neutrophil matrix metalloproteinase-9 in human plasma. Anal Biochem. 2003;322:283-286. 6.Souza-Tarla CD, Uzuelli JA, Machado AA, et al. Methodological issues affecting the determination of plasma matrix metalloproteinase (MMP)-2 and MMP-9 activities. Clin Biochem. 2005;38:410-414 7.Tanus-Santos JE, Gerlach RF. Circulating Matrix Metalloproteinase-9 Levels as a Possible Marker of Aortic Stiffness. Arterioscler Thromb Vasc Biol. 2005;25:e27 |
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