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.

Four-Gene Pan-African Blood Signature Predicts Progression to Tuberculosis

“…Such prognostic biomarkers would have the most impact in point-of-care tests for resource-limited settings, such as those in Sub-Saharan Africa. Test performance should not be adversely affected by diversity of ethnic background (16) and circulating Mtb lineage (17), as seen in Africa. A TB risk test must be practical for field application and therefore based on accessible biological samples routinely used in clinical settings, such as peripheral blood (18).…”

Tuberculosis, Pulmonary Cavitation, and Matrix Metalloproteinases

“…TB meningitis, the most severe form of TB infection, is associated with increased MMP-9 concentrations and decreased with antituberculous treatment (63). MMP-1 was found to be an immunological correlate of delayed M.tb sputum conversion in African and Eurasian ancestry (64), whereas vitamin D, a recognized adjunctive therapy in human TB, suppressed MMP-7 and -9 secretion (65).…”

Extrapulmonary tuberculosis among immigrants in a low-TB burden and high immigrant receiving city of northern Italy

“…The fact that data suggested a role of subjects' origin in TB development could be linked to genetic factors related to the host, or to the bacteria (tubercular lineages), or both [12,23,24].…”