Browsing by Author "Duffy, Darragh"

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    Immune profiling enables stratification of patients with active tuberculosis disease or mycobacterium tuberculosis infection
    (Oxford University Press, 2020-10) Duffy, Darragh; Nemes, Elisa; Llibre, Alba; Rouilly, Vincent; Musvosvi, Munyaradzi; Smith, Nikaïa; Filander, Elizabeth; Africa, Hadn; Mabwe, Simbarashe; Jaxa, Lungisa; Charbit, Bruno; Mulenga, Humphrey; Tameris, Michele; Walzl, Gerhard; Malherbe, Stephanus; Thomas, Stephanie; Hatherill, Mark; Bilek, Nicole; Scriba, Thomas J.; Albert, Matthew L.
    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 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.