title: 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.
authors.affiliation: Division of Mycobacterial Research, MRC National Institute for Medical Research, London, United Kingdom.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Coussens
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wilkinson
authors.forename: Vladyslav
authors.initials: V
authors.lastname: Nikolayevskyy
authors.forename: Paul T
authors.initials: PT
authors.lastname: Elkington
authors.forename: Yasmeen
authors.initials: Y
authors.lastname: Hanifa
authors.forename: Kamrul
authors.initials: K
authors.lastname: Islam
authors.forename: Peter M
authors.initials: PM
authors.lastname: Timms
authors.forename: Graham H
authors.initials: GH
authors.lastname: Bothamley
authors.forename: Alleyna P
authors.initials: AP
authors.lastname: Claxton
authors.forename: Geoffrey E
authors.initials: GE
authors.lastname: Packe
authors.forename: Mathina
authors.initials: M
authors.lastname: Darmalingam
authors.forename: Robert N
authors.initials: RN
authors.lastname: Davidson
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Milburn
authors.forename: Lucy V
authors.initials: LV
authors.lastname: Baker
authors.forename: Richard D
authors.initials: RD
authors.lastname: Barker
authors.forename: Francis A
authors.initials: FA
authors.lastname: Drobniewski
authors.forename: Charles A
authors.initials: CA
authors.lastname: Mein
authors.forename: Leena
authors.initials: L
authors.lastname: Bhaw-Rosun
authors.forename: Rosamond A
authors.initials: RA
authors.lastname: Nuamah
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Griffiths
authors.forename: Adrian R
authors.initials: AR
authors.lastname: Martineau
mesh_terms: D000328:Adult; D000904:Antibiotics, Antitubercular / Q000627:therapeutic use; D000942:Antigens, Bacterial / Q000378:metabolism; D044466:Asian People; D058491:Bacterial Load / Q000187:drug effects; D044383:Black People; D001773:Blood Cells / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood* / Q000378:metabolism; D007538:Isoniazid / Q000627:therapeutic use; D008131:London; D008297:Male; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000276:immunology* / Q000302:isolation & purification; D013183:Sputum / Q000187:drug effects / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000208:ethnology / Q000276:immunology* / Q000821:virology; D044465:White People; D055815:Young Adult
chemical_list: D000904:Antibiotics, Antitubercular; D000942:Antigens, Bacterial; D018836:Inflammation Mediators; D007538:Isoniazid