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Measurement of the noncomplexed free fraction of tissue inhibitor of metalloproteinases I in plasma by immunoassay

Holten-Andersen, MN; Christensen, IJ; Nielsen, HJ; Lilja, Hans LU ; Murphy, G; Jensen, V; Brunner, N and Piironen, T (2002) In Clinical Chemistry 48(8). p.1305-1313
Abstract
Background: We previously found differences in total concentrations of tissue inhibitor of metalloproteinases 1 (TIMP-1) in plasma from donors and cancer patients. Because TIMP-1 can exist in more than one molecular form, a new immunoassay to specifically detect free TIMP-1 was developed and concentrations were determined in plasma from healthy donors and colorectal cancer (CRC) patients. Methods: We established and validated an immunoassay for the specific measurement of free TIMP-1 that uses a polyclonal anti-TIMP-1 antibody for capture and a monoclonal anti-TIMP-1 antibody that binds only free TIMP-1 for detection of antigen. Plasma samples from healthy donors and CRC patients were assayed for free TIMP-1. Total TIMP-1 was measured by... (More)
Background: We previously found differences in total concentrations of tissue inhibitor of metalloproteinases 1 (TIMP-1) in plasma from donors and cancer patients. Because TIMP-1 can exist in more than one molecular form, a new immunoassay to specifically detect free TIMP-1 was developed and concentrations were determined in plasma from healthy donors and colorectal cancer (CRC) patients. Methods: We established and validated an immunoassay for the specific measurement of free TIMP-1 that uses a polyclonal anti-TIMP-1 antibody for capture and a monoclonal anti-TIMP-1 antibody that binds only free TIMP-1 for detection of antigen. Plasma samples from healthy donors and CRC patients were assayed for free TIMP-1. Total TIMP-1 was measured by our previously published assay. Results: The mean (SD) concentrations of free TIMP-1 were similar in citrate [55.5 (11.5) mug/L] and EDTA plasma [58.9 (13.3) mug/L] from 76 donors (r(2) = 0.82). In 154 donors, the ratio of free TIMP-1 [mean (SD), 64.5 (18.0) mug/L] to total TIMP-1 [83.8 (19.8) mug/L] in EDTA plasma was 0.77. Plasma concentrations of free and total TIMP-1 correlated significantly to age (free, r(2) = 0.19; total, r(2) = .0.27; P < 0.0001), increasing 50% over an age span of 45 years. Free and total TIMP-1 were significantly increased in CRC patients (P < 0.0001), whereas the ratio of free to total TIMP-1 (mean, 0.58) was significantly lower than in donors. Conclusions: Most of the TIMP-1 in donor plasma is present in its free form, and free TIMP-1 increases with age. Free and total TIMP-1 are increased in CRC patient plasma, but the ratio of free to total TIMP-1 is significantly lower in these patients than in donors. (C) 2002 American Association for Clinical Chemistry. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Clinical Chemistry
volume
48
issue
8
pages
1305 - 1313
publisher
American Association for Clinical Chemistry
external identifiers
  • wos:000176996500024
  • pmid:12142388
  • scopus:0036326571
ISSN
0009-9147
language
English
LU publication?
yes
id
52fcc324-9afd-427c-979a-3e4f006cbca0 (old id 892917)
alternative location
http://www.clinchem.org/cgi/reprint/48/8/1305
date added to LUP
2008-01-23 15:39:15
date last changed
2017-07-23 03:39:41
@article{52fcc324-9afd-427c-979a-3e4f006cbca0,
  abstract     = {Background: We previously found differences in total concentrations of tissue inhibitor of metalloproteinases 1 (TIMP-1) in plasma from donors and cancer patients. Because TIMP-1 can exist in more than one molecular form, a new immunoassay to specifically detect free TIMP-1 was developed and concentrations were determined in plasma from healthy donors and colorectal cancer (CRC) patients. Methods: We established and validated an immunoassay for the specific measurement of free TIMP-1 that uses a polyclonal anti-TIMP-1 antibody for capture and a monoclonal anti-TIMP-1 antibody that binds only free TIMP-1 for detection of antigen. Plasma samples from healthy donors and CRC patients were assayed for free TIMP-1. Total TIMP-1 was measured by our previously published assay. Results: The mean (SD) concentrations of free TIMP-1 were similar in citrate [55.5 (11.5) mug/L] and EDTA plasma [58.9 (13.3) mug/L] from 76 donors (r(2) = 0.82). In 154 donors, the ratio of free TIMP-1 [mean (SD), 64.5 (18.0) mug/L] to total TIMP-1 [83.8 (19.8) mug/L] in EDTA plasma was 0.77. Plasma concentrations of free and total TIMP-1 correlated significantly to age (free, r(2) = 0.19; total, r(2) = .0.27; P &lt; 0.0001), increasing 50% over an age span of 45 years. Free and total TIMP-1 were significantly increased in CRC patients (P &lt; 0.0001), whereas the ratio of free to total TIMP-1 (mean, 0.58) was significantly lower than in donors. Conclusions: Most of the TIMP-1 in donor plasma is present in its free form, and free TIMP-1 increases with age. Free and total TIMP-1 are increased in CRC patient plasma, but the ratio of free to total TIMP-1 is significantly lower in these patients than in donors. (C) 2002 American Association for Clinical Chemistry.},
  author       = {Holten-Andersen, MN and Christensen, IJ and Nielsen, HJ and Lilja, Hans and Murphy, G and Jensen, V and Brunner, N and Piironen, T},
  issn         = {0009-9147},
  language     = {eng},
  number       = {8},
  pages        = {1305--1313},
  publisher    = {American Association for Clinical Chemistry},
  series       = {Clinical Chemistry},
  title        = {Measurement of the noncomplexed free fraction of tissue inhibitor of metalloproteinases I in plasma by immunoassay},
  volume       = {48},
  year         = {2002},
}