Ethnic Variation in Inflammatory Profile in Tuberculosis

PLoS Pathogens

Yasmeen Hanifa¹  Lucy V. Baker²  Francis A. Drobniewski³  Richard D. Barker⁴  Robert N. Davidson⁵  Vladyslav Nikolayevskyy⁶  Anna K. Coussens⁷  Robert J. Wilkinson⁷  Rosamond A. Nuamah⁸  Christopher J. Griffiths⁸  Leena Bhaw-Rosun⁸  Graham H. Bothamley⁹  Geoffrey E. Packe⁹  Alleyna P. Claxton⁹  Mathina Darmalingam^1,10  Adrian R. Martineau^1,11  Charles A. Mein^1,11  Kamrul Islam^1,11  Peter M. Timms^1,11  Paul T. Elkington^1,11  Heather J. Milburn^1,12 

[1] Department of Infectious Diseases and Immunity, Imperial College, London, United Kingdom;Department of Respiratory Medicine, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom;Department of Respiratory Medicine, Kings College Hospital, London, United Kingdom;Department of Respiratory Medicine, Lewisham Hospital, London, United Kingdom;Department of Respiratory Medicine, Whipps Cross University Hospital, London, United Kingdom;Division of Medicine, Imperial College London, London, United Kingdom;Division of Mycobacterial Research, MRC National Institute for Medical Research, London, United Kingdom;Genome Centre, Queen Mary University of London, Barts and The London School of Medicine, London, United Kingdom;Homerton University NHS Foundation Trust, London, United Kingdom;Newham Chest Clinic, Forest Gate, London, United Kingdom;Queen Mary University of London, Barts and The London School of Medicine and Dentistry, Blizard Institute, London, United Kingdom;Tuberculosis Clinic, Northwick Park Hospital, Harrow, United Kingdom

关键词: African people;    Inflammation;    Mycobacterium tuberculosis;    Sputum;    Vitamin D;    Immune response;    Principal component analysis;    Tuberculosis;   

DOI  :  10.1371/journal.ppat.1003468

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY