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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Ethnic Variation in Inflammatory Profile in Tuberculosis
PLoS Pathogens, Volume 9, No. 7, Article e1003468, Year 2013
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Description
Distinct phylogenetic lineages of Mycobacterium tuberculosis (MTB) cause disease in patients of particular genetic ancestry, and elicit different patterns of cytokine and chemokine secretion when cultured with human macrophages in vitro. Circulating and antigen-stimulated concentrations of these inflammatory mediators might therefore be expected to vary significantly between tuberculosis patients of different ethnic origin. Studies to characterise such variation, and to determine whether it relates to host or bacillary factors, have not been conducted. We therefore compared circulating and antigen-stimulated concentrations of 43 inflammatory mediators and 14 haematological parameters (inflammatory profile) in 45 pulmonary tuberculosis patients of African ancestry vs. 83 patients of Eurasian ancestry in London, UK, and investigated the influence of bacillary and host genotype on these profiles. Despite having similar demographic and clinical characteristics, patients of differing ancestry exhibited distinct inflammatory profiles at presentation: those of African ancestry had lower neutrophil counts, lower serum concentrations of CCL2, CCL11 and vitamin D binding protein (DBP) but higher serum CCL5 concentrations and higher antigen-stimulated IL-1 receptor antagonist and IL-12 secretion. These differences associated with ethnic variation in host DBP genotype, but not with ethnic variation in MTB strain. Ethnic differences in inflammatory profile became more marked following initiation of antimicrobial therapy, and immunological correlates of speed of elimination of MTB from the sputum differed between patients of African vs. Eurasian ancestry. Our study demonstrates a hitherto unappreciated degree of ethnic heterogeneity in inflammatory profile in tuberculosis patients that associates primarily with ethnic variation in host, rather than bacillary, genotype. Candidate immunodiagnostics and immunological biomarkers of response to antimicrobial therapy should be derived and validated in tuberculosis patients of different ethnic origin. © 2013 Coussens et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3701709/bin/ppat.1003468.s001.ppt
https://efashare.b-cdn.net/share/pmc/articles/PMC3701709/bin/ppat.1003468.s002.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3701709/bin/ppat.1003468.s003.docx
https://efashare.b-cdn.net/share/pmc/articles/PMC3701709/bin/ppat.1003468.s004.docx
https://efashare.b-cdn.net/share/pmc/articles/PMC3701709/bin/ppat.1003468.s005.docx
https://efashare.b-cdn.net/share/pmc/articles/PMC3701709/bin/ppat.1003468.s006.docx
Authors & Co-Authors
Coussens, Anna K.
United Kingdom, London
Mrc National Institute for Medical Research
Wilkinson, Robert J.
United Kingdom, London
Mrc National Institute for Medical Research
United Kingdom, London
Imperial College London
Nikolayevskyy, Vladyslav N.
United Kingdom, London
Queen Mary University of London
Elkington, Paul
United Kingdom, London
Imperial College London
Hanifa, Yasmeen
United Kingdom, London
Queen Mary University of London
Timms, Peter Mc Lean
United Kingdom, London
Homerton University Hospital Nhs Foundation Trust
Bothamley, Graham Henry
United Kingdom, London
Homerton University Hospital Nhs Foundation Trust
Packe, Geoffrey E.
United Kingdom, London
Newham Chest Clinic
Davidson, Robert N.
United Kingdom, Harrow
Northwick Park Hospital
Milburn, Heather June
United Kingdom, London
Guy's and st Thomas' Nhs Foundation Trust
Barker, Richard D.
United Kingdom, London
King's College Hospital
Drobniewski, Francis A.
United Kingdom, London
Queen Mary University of London
Mein, Charles A.
United Kingdom, London
Queen Mary University of London
Griffiths, Christopher J.
United Kingdom, London
Queen Mary University of London
Martineau, Adrian R.
United Kingdom, London
Mrc National Institute for Medical Research
United Kingdom, London
Imperial College London
United Kingdom, London
Queen Mary University of London
Statistics
Citations: 65
Authors: 15
Affiliations: 10
Identifiers
Doi:
10.1371/journal.ppat.1003468
ISSN:
15537374
Research Areas
Genetics And Genomics