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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:e17.)
© 2008 American Heart Association, Inc.

Letters to the Editor

Matrix Metalloproteinase-8 and Tissue Inhibitor of Metalloproteinase-1 in Serum Do Not Reflect the Analytes Circulating in Blood

A.M. Tuomainen

Institute of Dentistry, University of Helsinki, Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, Finland

K. Nyyssönen

Research Institute of Public Health, University of Kuopio, Finland

T. Tervahartiala; T. Sorsa; P.J. Pussinen

Institute of Dentistry, University of Helsinki, Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, Finland

Key Words: matrix metalloproteinase-8 • time-resolved immunofluorometric assay • enzyme-linked immunosorbent assay • serum • plasma

In response:

We appreciate the interest of Professor Jung¹ in our article. He raises an important issue concerning the methods of collecting blood samples for assay determinations and points out the differences between serum and plasma matrix metalloproteinase (MMP)-8 measurements. The serum samples used in our study were collected in vacuum glass tubes (Venoject VT-100 Terumo Corp) as previously described in detail.² Clotting in glass tubes is faster and more effective than in plastic tubes, and thus no clot activator was used. Unfortunately, no plasma samples were available for our studies.³

We are aware of the differences of the MMP-8 concentrations between serum and plasma samples. The Figure shows the MMP-8 concentrations of 15 serum and plasma samples from patients with chronic adult periodontitis.⁴ For determinations we use both time-resolved immunofluorometric assay, IFMA (Medix Biochemica) with monoclonal catching and tracer antibodies as in the original article, and ELISA (GE Healthcare, Amersham MMP-8 Human Biotrak ELISA System). As shown in the Figure, both methods gave significantly higher serum MMP-8 values compared with plasma samples from the same patients. The differences between serum IFMA and ELISA results may be explained by the high sensitivity of IFMA, and by the obviously different specificities of the antibodies used in the assays. The differences were most notable with high serum MMP-8 concentrations as measured by IFMA (>20 ng/mL), whereas smaller concentrations gave similar results with both procedures (data not shown). Most importantly, there were significant positive correlations between serum and plasma IFMA (r=0.636, P=0.015) as well as between serum and plasma ELISA (r=0.718, P=0.003) measurements.

View larger version (19K): [in this window] [in a new window]   Figure. Plasma and serum MMP-8 concentrations from 15 patients with chronic periodontitis as measured with IFMA and ELISA. Median and interquartile range are shown.

We agree with Professor Jung that it is crucial to know what kind of method is used in collecting blood samples before determinations. In addition, we emphasize the importance of the selection of assay. However, the aim of our study³ was to evaluate the association of serum MMP-8 with cardiovascular diseases (CVD), irrespective of the origin of the protein. Serum concentrations may reflect the overall homeostasis of MMP-8, and therefore we consider our conclusion of its prognostic and diagnostic value concerning CVD still to be valid.

Acknowledgments

We thank Ritva Keva for excellent technical assistance.

Disclosures

None.

References

1. Jung K. Matrix. Metalloproteinase-8 and tissue inhibitor of metalloproteinase-1 in serum do not reflect the analytes circulating in blood. Arterioscler Thromb Vasc Biol. 2008; 28: •••–•••.

2. Salonen JT, Salonen R, Seppänen K, Rauramaa R, Tuomilehto J. HDL, HDL2, and HDL3 subfractions, and the risk of acute myocardial infarction: a prospective population study in eastern Finnish men. Circulation. 1991; 84: 129–139.[Abstract/Free Full Text]

3. Tuomainen AM, Nyyssönen K, Laukkanen JA, Tervahartiala T, Tuomainen TP, Salonen JT, Sorsa T, Pussinen PJ. Serum matrix metalloproteinase-8 concentrations are associated with cardiovascular outcome in men. Arterioscler Thromb Vasc Biol. 2007; 27: 2722–2728.[Abstract/Free Full Text]

4. Mäntylä P, Stenman M, Kinane DF, Salo T, Suomalainen K, Tikanoja S, Sorsa T. Monitoring periodontal disease status in smokers and nonsmokers using a gingival crevicular fluid matrix metalloproteinase-8-specific chair-side test. J Periodontal Res. 2006; 41: 503–512.[CrossRef][Medline] [Order article via Infotrieve]

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