Measurement of the noncomplexed free fraction of tissue inhibitor of metalloproteinases I in plasma by immunoassay
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/892917
- author
- Holten-Andersen, MN ; Christensen, IJ ; Nielsen, HJ ; Lilja, Hans LU ; Murphy, G ; Jensen, V ; Brunner, N and Piironen, T
- organization
- publishing date
- 2002
- 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
- 2016-04-01 11:47:39
- date last changed
- 2022-01-26 18:19:00
@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 < 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.}}, 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}}, url = {{http://www.clinchem.org/cgi/reprint/48/8/1305}}, volume = {{48}}, year = {{2002}}, }