title: Gender-dependent differences in plasma matrix metalloproteinase-8 elevated in pulmonary tuberculosis.
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.
authors: Infectious Diseases and Immunity, Imperial College London, London, United Kingdom.
authors: Tarangini
authors: T
authors: Sathyamoorthy
authors: Infectious Diseases and Immunity, Imperial College London, London, United Kingdom.
authors: Gurjinder
authors: G
authors: Sandhu
authors: NIHR Southampton Respiratory Biomedical Research Unit, Clinical and Experimental Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors: Liku B
authors: LB
authors: Tezera
authors: The Royal London Hospital, Whitechapel, United Kingdom.
authors: Richard
authors: R
authors: Thomas
authors: NIHR Southampton Respiratory Biomedical Research Unit, Clinical and Experimental Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors: Akul
authors: A
authors: Singhania
authors: NIHR Southampton Respiratory Biomedical Research Unit, Clinical and Experimental Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors: Christopher H
authors: CH
authors: Woelk
authors: NIHR Southampton Respiratory Biomedical Research Unit, Clinical and Experimental Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; Primary Care and Population Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors: Borislav D
authors: BD
authors: Dimitrov
authors: Infectious Diseases and Immunity, Imperial College London, London, United Kingdom; Brighton and Sussex University Hospitals NHS Trust, Brighton, United Kingdom.
authors: Dan
authors: D
authors: Agranoff
authors: Infectious Diseases and Immunity, Imperial College London, London, United Kingdom; Microbiology, Universidad Cayetano Heredia, Lima, Peru.
authors: Carlton A W
authors: CA
authors: Evans
authors: Infectious Diseases and Immunity, Imperial College London, London, United Kingdom.
authors: Jon S
authors: JS
authors: Friedland
authors: Infectious Diseases and Immunity, Imperial College London, London, United Kingdom; NIHR Southampton Respiratory Biomedical Research Unit, Clinical and Experimental Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; Institute for Life Sciences, University of Southampton, Southampton, United Kingdom.
authors: Paul T
authors: PT
authors: Elkington
mesh_terms: D000328:Adult; D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood; D020784:Matrix Metalloproteinase 8 / Q000097:blood*; D008875:Middle Aged; D015999:Multivariate Analysis; D009504:Neutrophils / Q000201:enzymology; D025341:Principal Component Analysis; D012727:Sex Characteristics; D014397:Tuberculosis, Pulmonary / Q000097:blood* / Q000201:enzymology*; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D020784:Matrix Metalloproteinase 8; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1
references: Respir Res. 2001;2(1):10-9
references: 11686860
references: Int J Tuberc Lung Dis. 2002 Aug;6(8):713-9
references: 12150484
references: Am J Respir Crit Care Med. 2003 Feb 15;167(4):593-8
references: 12588713
references: Lancet. 2003 Sep 13;362(9387):887-99
references: 13678977
references: J Clin Invest. 1989 Nov;84(5):1395-402
references: 2553773
references: Eur Respir J. 1990 Oct;3(9):1048-63
references: 2289553
references: Chest. 1995 Jun;107(6):1641-7
references: 7781360
references: N Engl J Med. 1995 Jul 27;333(4):222-7
references: 7791838
references: Eur Respir J. 1996 Oct;9(10):2031-5
references: 8902463
references: Int J Tuberc Lung Dis. 1997 Aug;1(4):352-7
references: 9432392
references: Lancet. 1999 Mar 20;353(9157):1000-1
references: 10459926
references: Clin Chim Acta. 2005 Feb;352(1-2):209-15
references: 15653116
references: Thorax. 2006 Apr;61(4):348-53
references: 16449260
references: Immunol Res. 2006;34(3):177-92
references: 16891670
references: Int J Tuberc Lung Dis. 2007 Feb;11(2):233-6
references: 17263297
references: Am J Reprod Immunol. 2007 Aug;58(2):111-9
references: 17631004
references: J Cell Physiol. 2007 Nov;213(2):355-64
references: 17654499
references: Arterioscler Thromb Vasc Biol. 2008 Apr;28(4):611-4
references: 18354094
references: PLoS Med. 2009 Dec;6(12):e1000199
references: 20027210
references: Chest. 2010 Jan;137(1):122-8
references: 19749004
references: Science. 2010 Jan 22;327(5964):466-9
references: 20007864
references: Nature. 2010 Aug 19;466(7309):973-7
references: 20725040
references: Sci Transl Med. 2011 Feb 23;3(71):71ps6
references: 21346167
references: Nat Rev Immunol. 2011 May;11(5):343-54
references: 21475309
references: J Clin Invest. 2011 May;121(5):1827-33
references: 21519144
references: Thorax. 2012 Apr;67(4):286-8
references: 22427352
references: Am J Respir Crit Care Med. 2012 May 1;185(9):989-97
references: 22345579
references: PLoS One. 2012;7(5):e38080
references: 22666453
references: Clin Chem Lab Med. 2012 Mar;50(3):449-54
references: 22107133
references: Med Sci Monit. 2012 Aug;18(8):CR500-505
references: 22847199
references: Hum Immunol. 2012 Oct;73(10):985-91
references: 22820625
references: PLoS One. 2013;8(4):e61333
references: 23613834
references: PLoS One. 2013;8(4):e61002
references: 23637781
references: PLoS One. 2013;8(4):e62390
references: 23638062
references: J Infect Dis. 2013 Nov 15;208(10):1571-9
references: 23922364
references: Eur J Immunol. 2014 Jan;44(1):127-36
references: 24136296
references: Int J Equity Health. 2014;13:32
references: 24767610
references: J Infect Dis. 2014 Jul 15;209 Suppl 3:S100-6
references: 24966189
references: Arthritis Res Ther. 2012;14(5):R204
references: 23031278