Ethnic variation in inflammatory profile in tuberculosis.
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 inf...
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Public Library of Science (PLoS)
2013
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oai:doaj.org-article:4a0183781eb747bc9c277014a76445352021-11-18T06:05:25ZEthnic variation in inflammatory profile in tuberculosis.1553-73661553-737410.1371/journal.ppat.1003468https://doaj.org/article/4a0183781eb747bc9c277014a76445352013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23853590/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Distinct 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.Anna K CoussensRobert J WilkinsonVladyslav NikolayevskyyPaul T ElkingtonYasmeen HanifaKamrul IslamPeter M TimmsGraham H BothamleyAlleyna P ClaxtonGeoffrey E PackeMathina DarmalingamRobert N DavidsonHeather J MilburnLucy V BakerRichard D BarkerFrancis A DrobniewskiCharles A MeinLeena Bhaw-RosunRosamond A NuamahChristopher J GriffithsAdrian R MartineauPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 7, p e1003468 (2013) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
| spellingShingle |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Anna K Coussens Robert J Wilkinson Vladyslav Nikolayevskyy Paul T Elkington Yasmeen Hanifa Kamrul Islam Peter M Timms Graham H Bothamley Alleyna P Claxton Geoffrey E Packe Mathina Darmalingam Robert N Davidson Heather J Milburn Lucy V Baker Richard D Barker Francis A Drobniewski Charles A Mein Leena Bhaw-Rosun Rosamond A Nuamah Christopher J Griffiths Adrian R Martineau Ethnic variation in inflammatory profile in tuberculosis. |
| 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. |
| format |
article |
| author |
Anna K Coussens Robert J Wilkinson Vladyslav Nikolayevskyy Paul T Elkington Yasmeen Hanifa Kamrul Islam Peter M Timms Graham H Bothamley Alleyna P Claxton Geoffrey E Packe Mathina Darmalingam Robert N Davidson Heather J Milburn Lucy V Baker Richard D Barker Francis A Drobniewski Charles A Mein Leena Bhaw-Rosun Rosamond A Nuamah Christopher J Griffiths Adrian R Martineau |
| author_facet |
Anna K Coussens Robert J Wilkinson Vladyslav Nikolayevskyy Paul T Elkington Yasmeen Hanifa Kamrul Islam Peter M Timms Graham H Bothamley Alleyna P Claxton Geoffrey E Packe Mathina Darmalingam Robert N Davidson Heather J Milburn Lucy V Baker Richard D Barker Francis A Drobniewski Charles A Mein Leena Bhaw-Rosun Rosamond A Nuamah Christopher J Griffiths Adrian R Martineau |
| author_sort |
Anna K Coussens |
| title |
Ethnic variation in inflammatory profile in tuberculosis. |
| title_short |
Ethnic variation in inflammatory profile in tuberculosis. |
| title_full |
Ethnic variation in inflammatory profile in tuberculosis. |
| title_fullStr |
Ethnic variation in inflammatory profile in tuberculosis. |
| title_full_unstemmed |
Ethnic variation in inflammatory profile in tuberculosis. |
| title_sort |
ethnic variation in inflammatory profile in tuberculosis. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/4a0183781eb747bc9c277014a7644535 |
| work_keys_str_mv |
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