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Gender-dependent differences in plasma matrix metalloproteinase-8 elevated in pulmonary tuberculosis

Gender-dependent differences in plasma matrix metalloproteinase-8 elevated in pulmonary tuberculosis
Gender-dependent differences in plasma matrix metalloproteinase-8 elevated in pulmonary tuberculosis
Tuberculosis (TB) remains a global health pandemic and greater understanding of underlying pathogenesis is required to develop novel therapeutic and diagnostic approaches. Matrix metalloproteinases (MMPs) are emerging as key effectors of tissue destruction in TB but have not been comprehensively studied in plasma, nor have gender differences been investigated. We measured the plasma concentrations of MMPs in a carefully characterised, prospectively recruited clinical cohort of 380 individuals. The collagenases, MMP-1 and MMP-8, were elevated in plasma of patients with pulmonary TB relative to healthy controls, and MMP-7 (matrilysin) and MMP-9 (gelatinase B) were also increased. MMP-8 was TB-specific (p<0.001), not being elevated in symptomatic controls (symptoms suspicious of TB but active disease excluded). Plasma MMP-8 concentrations inversely correlated with body mass index. Plasma MMP-8 concentration was 1.51-fold higher in males than females with TB (p<0.05) and this difference was not due to greater disease severity in men. Gender-specific analysis of MMPs demonstrated consistent increase in MMP-1 and -8 in TB, but MMP-8 was a better discriminator for TB in men. Plasma collagenases are elevated in pulmonary TB and differ between men and women. Gender must be considered in investigation of TB immunopathology and development of novel diagnostic markers.
1932-6203
1-15
Sathyamoorthy, Tarangini
0217c808-371e-4292-a33d-0082d4e681d5
Sandhu, Gurjinder
f3fbde68-10b9-4ea4-9115-228f7d0e8c8c
Tezera, Liku B.
e64520b0-6de3-4d53-9a35-67954fb876bc
Thomas, Richard
55b35482-1f51-4768-af49-29856ff52093
Singhania, Akul
286731e9-f6a8-4392-9ac5-71c7e4c3aab7
Woelk, Christopher H.
4d3af0fd-658f-4626-b3b5-49a6192bcf7d
Dimitrov, Borislav D.
366d715f-ffd9-45a1-8415-65de5488472f
Agranoff, Dan
8cd1290a-6ef7-4cdf-918a-251a5ec56521
Evans, Carlton A.W.
8ac2fab5-614b-4da4-8ba8-81b6ef835d49
Friedland, Jon S.
9968669f-afe0-4163-9b35-3b476246fd4a
Elkington, Paul T.
60828c7c-3d32-47c9-9fcc-6c4c54c35a15
Sathyamoorthy, Tarangini
0217c808-371e-4292-a33d-0082d4e681d5
Sandhu, Gurjinder
f3fbde68-10b9-4ea4-9115-228f7d0e8c8c
Tezera, Liku B.
e64520b0-6de3-4d53-9a35-67954fb876bc
Thomas, Richard
55b35482-1f51-4768-af49-29856ff52093
Singhania, Akul
286731e9-f6a8-4392-9ac5-71c7e4c3aab7
Woelk, Christopher H.
4d3af0fd-658f-4626-b3b5-49a6192bcf7d
Dimitrov, Borislav D.
366d715f-ffd9-45a1-8415-65de5488472f
Agranoff, Dan
8cd1290a-6ef7-4cdf-918a-251a5ec56521
Evans, Carlton A.W.
8ac2fab5-614b-4da4-8ba8-81b6ef835d49
Friedland, Jon S.
9968669f-afe0-4163-9b35-3b476246fd4a
Elkington, Paul T.
60828c7c-3d32-47c9-9fcc-6c4c54c35a15

Sathyamoorthy, Tarangini, Sandhu, Gurjinder, Tezera, Liku B., Thomas, Richard, Singhania, Akul, Woelk, Christopher H., Dimitrov, Borislav D., Agranoff, Dan, Evans, Carlton A.W., Friedland, Jon S. and Elkington, Paul T. (2015) Gender-dependent differences in plasma matrix metalloproteinase-8 elevated in pulmonary tuberculosis. PLoS ONE, 10 (1), 1-15, [e0117605]. (doi:10.1371/journal.pone.0117605).

Record type: Article

Abstract

Tuberculosis (TB) remains a global health pandemic and greater understanding of underlying pathogenesis is required to develop novel therapeutic and diagnostic approaches. Matrix metalloproteinases (MMPs) are emerging as key effectors of tissue destruction in TB but have not been comprehensively studied in plasma, nor have gender differences been investigated. We measured the plasma concentrations of MMPs in a carefully characterised, prospectively recruited clinical cohort of 380 individuals. The collagenases, MMP-1 and MMP-8, were elevated in plasma of patients with pulmonary TB relative to healthy controls, and MMP-7 (matrilysin) and MMP-9 (gelatinase B) were also increased. MMP-8 was TB-specific (p<0.001), not being elevated in symptomatic controls (symptoms suspicious of TB but active disease excluded). Plasma MMP-8 concentrations inversely correlated with body mass index. Plasma MMP-8 concentration was 1.51-fold higher in males than females with TB (p<0.05) and this difference was not due to greater disease severity in men. Gender-specific analysis of MMPs demonstrated consistent increase in MMP-1 and -8 in TB, but MMP-8 was a better discriminator for TB in men. Plasma collagenases are elevated in pulmonary TB and differ between men and women. Gender must be considered in investigation of TB immunopathology and development of novel diagnostic markers.

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Accepted/In Press date: 29 December 2014
e-pub ahead of print date: 30 January 2015
Published date: 30 January 2015
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 374112
URI: http://eprints.soton.ac.uk/id/eprint/374112
ISSN: 1932-6203
PURE UUID: 43a582e7-856d-492e-a2ea-d23a6c31f8f5
ORCID for Paul T. Elkington: ORCID iD orcid.org/0000-0003-0390-0613

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Date deposited: 03 Feb 2015 15:22
Last modified: 18 Feb 2021 17:19

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Contributors

Author: Tarangini Sathyamoorthy
Author: Gurjinder Sandhu
Author: Liku B. Tezera
Author: Richard Thomas
Author: Akul Singhania
Author: Christopher H. Woelk
Author: Borislav D. Dimitrov
Author: Dan Agranoff
Author: Carlton A.W. Evans
Author: Jon S. Friedland

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