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Induced Sputum MMP-1, -3 & -8 concentrations during treatment of tuberculosis

Induced Sputum MMP-1, -3 & -8 concentrations during treatment of tuberculosis
Induced Sputum MMP-1, -3 & -8 concentrations during treatment of tuberculosis
INTRODUCTION:
Tuberculosis (TB) destroys lung tissues and this immunopathology is mediated in part by Matrix Metalloproteinases (MMPs). There are no data on the relationship between local tissue MMPs concentrations, anti-tuberculosis therapy and sputum conversion.

MATERIALS AND METHODS:
Induced sputum was collected from 68 TB patients and 69 controls in a cross-sectional study. MMPs concentrations were measured by Luminex array, TIMP concentrations by ELISA and were correlated with a disease severity score (TBscore). 46 TB patients were then studied longitudinally at the 2nd, 8th week and end of treatment.

RESULTS:
Sputum MMP-1,-2,-3,-8,-9 and TIMP-1 and -2 concentrations are increased in TB. Elevated MMP-1 and -3 concentrations are independently associated with higher TB severity scores (p<0.05). MMP-1, -3 and -8 concentrations decreased rapidly during treatment (p<0.05) whilst there was a transient increase in TIMP-1/2 concentrations at week 2. MMP-2, -8 and -9 and TIMP-2 concentrations were higher at TB diagnosis in patients who remain sputum culture positive at 2 weeks and MMP-3, -8 and TIMP-1 concentrations were higher in these patients at 2nd week of TB treatment.

CONCLUSIONS:
MMPs are elevated in TB patients and associate with disease severity. This matrix-degrading phenotype resolves rapidly with treatment. The MMP profile at presentation correlates with a delayed treatment response
1932-6203
e61333-[8pp]
Ugarte-Gil, C.A.
98659f30-42ac-4613-b8be-16afef6fbf65
Elkington, P.T.
60828c7c-3d32-47c9-9fcc-6c4c54c35a15
Gilman, R.
5f817303-42b5-4280-b7d8-fa25fc617efc
Coronel, J.
04d7e155-cb4b-4af7-b2a6-9d6b0acf98ab
Bernabe-Ortiz, A.
0d7328d0-c9bf-43ec-961c-25129b080d17
Gotuzzo, E.
25e518a5-3564-492b-94ef-d64631427bc6
Friedland, J.S.
e64a7af8-b969-4426-82e6-5ebe819799c9
Moore, D.A.J.
59761645-9ded-4ce5-bab6-b4a232de1a40
Ugarte-Gil, C.A.
98659f30-42ac-4613-b8be-16afef6fbf65
Elkington, P.T.
60828c7c-3d32-47c9-9fcc-6c4c54c35a15
Gilman, R.
5f817303-42b5-4280-b7d8-fa25fc617efc
Coronel, J.
04d7e155-cb4b-4af7-b2a6-9d6b0acf98ab
Bernabe-Ortiz, A.
0d7328d0-c9bf-43ec-961c-25129b080d17
Gotuzzo, E.
25e518a5-3564-492b-94ef-d64631427bc6
Friedland, J.S.
e64a7af8-b969-4426-82e6-5ebe819799c9
Moore, D.A.J.
59761645-9ded-4ce5-bab6-b4a232de1a40

Ugarte-Gil, C.A., Elkington, P.T., Gilman, R., Coronel, J., Bernabe-Ortiz, A., Gotuzzo, E., Friedland, J.S. and Moore, D.A.J. (2013) Induced Sputum MMP-1, -3 & -8 concentrations during treatment of tuberculosis. PLoS ONE, 8 (4), e61333-[8pp]. (doi:10.1371/journal.pone.0061333). (PMID:23613834)

Record type: Article

Abstract

INTRODUCTION:
Tuberculosis (TB) destroys lung tissues and this immunopathology is mediated in part by Matrix Metalloproteinases (MMPs). There are no data on the relationship between local tissue MMPs concentrations, anti-tuberculosis therapy and sputum conversion.

MATERIALS AND METHODS:
Induced sputum was collected from 68 TB patients and 69 controls in a cross-sectional study. MMPs concentrations were measured by Luminex array, TIMP concentrations by ELISA and were correlated with a disease severity score (TBscore). 46 TB patients were then studied longitudinally at the 2nd, 8th week and end of treatment.

RESULTS:
Sputum MMP-1,-2,-3,-8,-9 and TIMP-1 and -2 concentrations are increased in TB. Elevated MMP-1 and -3 concentrations are independently associated with higher TB severity scores (p<0.05). MMP-1, -3 and -8 concentrations decreased rapidly during treatment (p<0.05) whilst there was a transient increase in TIMP-1/2 concentrations at week 2. MMP-2, -8 and -9 and TIMP-2 concentrations were higher at TB diagnosis in patients who remain sputum culture positive at 2 weeks and MMP-3, -8 and TIMP-1 concentrations were higher in these patients at 2nd week of TB treatment.

CONCLUSIONS:
MMPs are elevated in TB patients and associate with disease severity. This matrix-degrading phenotype resolves rapidly with treatment. The MMP profile at presentation correlates with a delayed treatment response

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Published date: April 2013
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 355599
URI: http://eprints.soton.ac.uk/id/eprint/355599
ISSN: 1932-6203
PURE UUID: ee963101-7d1d-4c77-8888-9b990a01fa5b
ORCID for P.T. Elkington: ORCID iD orcid.org/0000-0003-0390-0613

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Date deposited: 03 Sep 2013 09:21
Last modified: 15 Mar 2024 03:43

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Contributors

Author: C.A. Ugarte-Gil
Author: P.T. Elkington ORCID iD
Author: R. Gilman
Author: J. Coronel
Author: A. Bernabe-Ortiz
Author: E. Gotuzzo
Author: J.S. Friedland
Author: D.A.J. Moore

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