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Immune profiling enables stratification of patients with active TB disease or M. tuberculosis infection

Abstract : Background 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 active TB patients and compared to LTBI donors. Mtb- specific antigens and live bacillus Calmette-Guerin (BCG) were used as stimuli, with direct comparison to QFT. Protein analyses were performed using conventional and digital ELISA, as well as Luminex. Results TruCulture showed discrimination of active TB cases from LTBI (p < 0.0001 AUC = 0.81) as compared to QFT (p = 0.45 AUC = 0.56), based on an IFNγ readout after Mtb antigen stimulation. This result was replicated in an independent cohort (AUC = 0.89). In exploratory analyses, TB stratification could be further improved by the Mtb Ag/BCG IFNγ ratio (p < 0.0001 AUC = 0.91). Finally, the combination of digital ELISA and transcriptional analysis showed that LTBI donors with high IFNγ clustered with TB patients, suggesting the possibility to identify sub-clinical disease. Conclusions TruCulture offers a next-generation solution for whole blood stimulation and immunomonitoring with the possibility to discriminate active and latent infection.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03036505
Contributor : Marie-Christine Vougny <>
Submitted on : Wednesday, December 2, 2020 - 4:44:44 PM
Last modification on : Monday, June 14, 2021 - 4:24:03 PM
Long-term archiving on: : Wednesday, March 3, 2021 - 7:58:14 PM

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Distributed under a Creative Commons Attribution 4.0 International License

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Darragh Duffy, Elisa Nemes, Alba Llibre, Vincent Rouilly, Munyaradzi Musvosvi, et al.. Immune profiling enables stratification of patients with active TB disease or M. tuberculosis infection. Clinical Infectious Diseases, Oxford University Press (OUP), 2020, ⟨10.1093/cid/ciaa1562⟩. ⟨pasteur-03036505⟩

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