Imperial College London
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DrWafaKhamri

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Senior Teaching Fellow
 
 
 
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Contact

 

w.khamri

 
 
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Location

 

Queen Elizabeth the Queen Mother Wing (QEQM)St Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Vergis:2016:10.1136/gutjnl-2015-310378,
author = {Vergis, N and Khamri, W and Beale, K and Sadiq, F and Aletrari, MO and Moore, C and Atkinson, SR and Bernsmeier, C and Possamai, L and Petts, G and Ryan, JM and Foxton, M and Hogan, B and Foster, GR and O'Brien, AJ and Ma, Y and Shawcross, D and Wendon, JA and Antoniades, CG and Thursz, MR},
doi = {10.1136/gutjnl-2015-310378},
journal = {Gut},
pages = {519--529},
title = {Defective monocyte oxidative burst predicts infection in alcoholic hepatitis and is associated with reduced expression of NADPH oxidase},
url = {http://dx.doi.org/10.1136/gutjnl-2015-310378},
volume = {66},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Objective In order to explain the increasedsusceptibility to serious infection in alcoholic hepatitis,we evaluated monocyte phagocytosis, aberrations ofassociated signalling pathways and their reversibility, andwhether phagocytic defects could predict subsequentinfection.Design Monocytes were identified from blood samplesof 42 patients with severe alcoholic hepatitis usingmonoclonal antibody to CD14. Phagocytosis andmonocyte oxidative burst (MOB) were measured ex vivousing flow cytometry, luminometry and bacterial killingassays. Defects were related to the subsequentdevelopment of infection. Intracellular signallingpathways were investigated using western blotting andPCR. Interferon-γ (IFN-γ) was evaluated for itstherapeutic potential in reversing phagocytic defects.Paired longitudinal samples were used to evaluate theeffect of in vivo prednisolone therapy.Results MOB, production of superoxide and bacterialkilling in response to Escherichia coli were markedlyimpaired in patients with alcoholic hepatitis.Pretreatment MOB predicted development of infectionwithin two weeks with sensitivity and specificity thatwere superior to available clinical markers. Accordingly,defective MOB was associated with death at 28 and90 days. Expression of the gp91phox subunit ofnicotinamide adenine dinucleotide phosphate (NADPH)oxidase was reduced in patients with alcoholic hepatitisdemonstrating defective MOB. Monocytes were refractoryto IFN-γ stimulation and showed high levels of anegative regulator of cytokine signalling, suppressor ofcytokine signalling-1. MOB was unaffected by 7 days invivo prednisolone therapy.Conclusions Monocyte oxidative burst and bacterialkilling is impaired in alcoholic hepatitis while bacterialuptake by phagocytosis is preserved. Defective MOB isassociated with reduced expression of NADPH oxidase inthese patients and predicts the development of infectionand death.
AU  - Vergis,N
AU  - Khamri,W
AU  - Beale,K
AU  - Sadiq,F
AU  - Aletrari,MO
AU  - Moore,C
AU  - Atkinson,SR
AU  - Bernsmeier,C
AU  - Possamai,L
AU  - Petts,G
AU  - Ryan,JM
AU  - Foxton,M
AU  - Hogan,B
AU  - Foster,GR
AU  - O'Brien,AJ
AU  - Ma,Y
AU  - Shawcross,D
AU  - Wendon,JA
AU  - Antoniades,CG
AU  - Thursz,MR
DO  - 10.1136/gutjnl-2015-310378
EP  - 529
PY  - 2016///
SN  - 1468-3288
SP  - 519
TI  - Defective monocyte oxidative burst predicts infection in alcoholic hepatitis and is associated with reduced expression of NADPH oxidase
T2  - Gut
UR  - http://dx.doi.org/10.1136/gutjnl-2015-310378
UR  - https://gut.bmj.com/content/66/3/519
UR  - http://hdl.handle.net/10044/1/27705
VL  - 66
ER  -
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