Immune profiling enables stratification of patients with active tuberculosis disease or mycobacterium tuberculosis infection

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dc.contributor.authorDuffy, Darraghen_ZA
dc.contributor.authorNemes, Elisaen_ZA
dc.contributor.authorLlibre, Albaen_ZA
dc.contributor.authorRouilly, Vincenten_ZA
dc.contributor.authorMusvosvi, Munyaradzien_ZA
dc.contributor.authorSmith, Nikaïaen_ZA
dc.contributor.authorFilander, Elizabethen_ZA
dc.contributor.authorAfrica, Hadnen_ZA
dc.contributor.authorMabwe, Simbarasheen_ZA
dc.contributor.authorJaxa, Lungisaen_ZA
dc.contributor.authorCharbit, Brunoen_ZA
dc.contributor.authorMulenga, Humphreyen_ZA
dc.contributor.authorTameris, Micheleen_ZA
dc.contributor.authorWalzl, Gerharden_ZA
dc.contributor.authorMalherbe, Stephanusen_ZA
dc.contributor.authorThomas, Stephanieen_ZA
dc.contributor.authorHatherill, Marken_ZA
dc.contributor.authorBilek, Nicoleen_ZA
dc.contributor.authorScriba, Thomas J.en_ZA
dc.contributor.authorAlbert, Matthew L.en_ZA
dc.date.accessioned2022-06-03T08:42:39Zen_ZA
dc.date.available2022-06-03T08:42:39Zen_ZA
dc.date.issued2020-10en_ZA
dc.descriptionCITATION: Duffy, D. et al. Immune profiling enables stratification of patients with active tuberculosis disease or mycobacterium tuberculosis infection. Clinical Infectious Diseases, 73(9):e3398–e3408, doi:10.1093/cid/ciaa1562en_ZA
dc.descriptionThe original publication is available at https://academic.oup.com/cid/en_ZA
dc.description.abstractBackground Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb) infection and is a major public health problem. Clinical challenges include the lack of a blood-based test for active disease. Current blood-based tests, such as QuantiFERON (QFT) do not distinguish active TB disease from asymptomatic Mtb infection. Methods We hypothesized that TruCulture, an immunomonitoring method for whole-blood stimulation, could discriminate active disease from latent Mtb infection (LTBI). We stimulated whole blood from patients with active TB and compared with LTBI donors. Mtb-specific antigens and live bacillus Calmette-Guérin (BCG) were used as stimuli, with direct comparison to QFT. Protein analyses were performed using conventional and digital enzyme-linked immunosorbent assay (ELISA), as well as Luminex. Results TruCulture showed discrimination of active TB cases from LTBI (P < .0001, AUC = .81) compared with QFT (P = .45, AUC = .56), based on an interferon γ (IFNγ) readout after Mtb antigen (Ag) stimulation. This result was replicated in an independent cohort (AUC = .89). In exploratory analyses, TB stratification could be further improved by the Mtb antigen to BCG IFNγ ratio (P < .0001, AUC = .91). Finally, the combination of digital ELISA and transcriptional analysis showed that LTBI donors with high IFNγ clustered with patients with TB, suggesting the possibility to identify subclinical disease. Conclusions TruCulture offers a next-generation solution for whole-blood stimulation and immunomonitoring with the possibility to discriminate active and latent infection.en_ZA
dc.description.urihttps://academic.oup.com/cid/article/73/9/e3398/5924452en_ZA
dc.description.versionPublishers versionen_ZA
dc.format.extent11 pagesen_ZA
dc.identifier.citationDuffy, D. et al. Immune profiling enables stratification of patients with active tuberculosis disease or mycobacterium tuberculosis infection. Clinical Infectious Diseases, 73(9):e3398–e3408, doi:10.1093/cid/ciaa1562en_ZA
dc.identifier.issn1537-6591 (online)en_ZA
dc.identifier.issn1058-4838 (print)en_ZA
dc.identifier.otherdoi:10.1093/cid/ciaa1562en_ZA
dc.identifier.urihttp://hdl.handle.net/10019.1/125309en_ZA
dc.language.isoen_ZAen_ZA
dc.publisherOxford University Pressen_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectTuberculosis -- Treatmenten_ZA
dc.subjectImmune profilingen_ZA
dc.subjectPatient stratificationen_ZA
dc.subjectCytokinesen_ZA
dc.subjectBiochemical markersen_ZA
dc.subjectMycobacterium tuberculosisen_ZA
dc.subjectPublic health administrationen_ZA
dc.titleImmune profiling enables stratification of patients with active tuberculosis disease or mycobacterium tuberculosis infectionen_ZA
dc.typeArticleen_ZA
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