Differential RD-1-specific IFN-γ host responses to diverse Mycobacterium tuberculosis strains in HIV-uninfected persons may be explained by genotypic variation in the ESX-1 region

Michele Tomasicchio, Jason Limberis, Ruben van der Merwe, Rachael Jacobson, Richard Meldau, Grant Theron, Mark Nicol, Rob Warren, Keertan Dheda

Research output: Contribution to journalArticle

Abstract

OBJECTIVES: Between-person variability in T-cell-specific interferon-gamma release assay (IGRA) responses and discordance between IGRA test formats are poorly understood.

METHODS: We evaluated the IFN-γ responses (QuantiFERON-TB Gold-In-Tube (QFT-GIT) TSPOT-TB) stratified according to the M.tb spoligotype of the culture isolate obtained from the same patients with confirmed active TB (n = 91). We further analysed differences within the RD-1-encoding ESX-1 region between the different strain types using whole genome sequencing.

RESULTS: In HIV uninfected patients TSPOT.TB and QFT-GIT IFN-γ responses were 5-fold (p < 0.01) and 2-fold higher (p < 0.05) for those infected with family 33 compared to the LAM strain (additionally, TSPOT.TB responses were 5.6-fold (p < 0.05) and 2.6-fold higher (p < 0.05) for the patients infected with the family 33 versus the X strain and Beijing versus the LAM strain, respectively). Multivariate analysis revealed that strain type (determined by spoligotyping) was independently associated with the magnitude of the IGRA response (varied by IGRA test type) and this is likely explained by variability in the ESX-1 region of M. tuberculosis (determined by next-generation sequencing).

CONCLUSIONS: These data have implications for the understanding of between-person heterogeneity in IGRA responses, M. tuberculosis-specific host immunity, and the discordance between different IGRA test formats.

Original languageEnglish
JournalInternational Journal of Infectious Diseases
DOIs
Publication statusE-pub ahead of print - 24 Apr 2020
Externally publishedYes

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Copyright © 2020. Published by Elsevier Ltd.

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