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Ethnic variation in inflammatory profile in tuberculosis.

Abstract：

: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.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Coussens AK,Wilkinson RJ,Nikolayevskyy V,Elkington PT,Hanifa Y,Islam K,Timms PM,Bothamley GH,Claxton AP,Packe GE,Darmalingam M,Davidson RN,Milburn HJ,Baker LV,Barker RD,Drobniewski FA,Mein CA,Bhaw-Rosun L,Nuamah RA,

doi

10.1371/journal.ppat.1003468

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

e1003468

issue

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-12-02002

journal_volume

pub_type

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Ethnic variation in inflammatory profile in tuberculosis.