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

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dc.contributor.authorTomasicchio, Micheleen_ZA
dc.contributor.authorLimberis, Jasonen_ZA
dc.contributor.authorvan der Merwe, Rubenen_ZA
dc.contributor.authorJacobson, Rachaelen_ZA
dc.contributor.authorMeldau, Richarden_ZA
dc.contributor.authorTheron, Granten_ZA
dc.contributor.authorNicol, Marken_ZA
dc.contributor.authorWarren, Roben_ZA
dc.contributor.authorDheda, Keertanen_ZA
dc.date.accessioned2022-09-14T09:22:13Zen_ZA
dc.date.available2022-09-14T09:22:13Zen_ZA
dc.date.issued2020-04en_ZA
dc.descriptionCITATION: Tomasicchio, M. et al. 2020. 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. International journal of infectious diseases, 96:240–243. doi:10.1016/j.ijid.2020.04.053en_ZA
dc.descriptionThe original publication is available at https://www.journals.elsevier.com/international-journal-of-infectious-diseasesen_ZA
dc.description.abstractObjectives: 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] and TSPOT-TB) stratified according to the Mycobacterium tuberculosis spoligotype of the culture isolate obtained from the same patients with confirmed active tuberculosis (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 Mycobacteriumtuberculosis (determined by next-generation sequencing). Conclusions: These data have implications for the understanding of between-person heterogeneity in IGRA responses, Mycobateriumtuberculosis-specific host immunity, and the discordance between different IGRA test formats.en_ZA
dc.description.urihttps://www.clinicalkey.com/#!/content/playContent/1-s2.0-S120197122030268X?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS120197122030268X%3Fshowall%3Dtrue&referrer=https:%2F%2Fpubmed.ncbi.nlm.nih.gov%2Fen_ZA
dc.description.versionPublishers versionen_ZA
dc.format.extent4 pagesen_ZA
dc.identifier.citationTomasicchio, M. et al. 2020. 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. International journal of infectious diseases, 96:240–243. doi:10.1016/j.ijid.2020.04.053en_ZA
dc.identifier.issn1878-3511 (online)en_ZA
dc.identifier.issn1201-9712 (print)en_ZA
dc.identifier.otherdoi:10.1016/j.ijid.2020.04.053en_ZA
dc.identifier.urihttp://hdl.handle.net/10019.1/125727en_ZA
dc.language.isoen_ZAen_ZA
dc.publisherElsevieren_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectMycobacterium tuberculosisen_ZA
dc.subjectInterferon-gamma release assayen_ZA
dc.subjectImmune responseen_ZA
dc.subjectMolecular microbiologyen_ZA
dc.subjectInterleukin-18en_ZA
dc.titleDifferential 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 regionen_ZA
dc.typeArticleen_ZA
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