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© Research
Publication : Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

Immune Profiling Enables Stratification of Patients With Active Tuberculosis Disease or Mycobacterium tuberculosis Infection.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America - 16 Oct 2020

Duffy D, Nemes E, Llibre A, Rouilly V, Musvosvi M, Smith N, Filander E, Africa H, Mabwe S, Jaxa L, Charbit B, Mulenga H, Tameris M, Walzl G, Malherbe S, Thomas S, Hatherill M, Bilek N, Scriba TJ, Albert ML

Link to Pubmed [PMID] – 33059361

Link to DOI – 10.1093/cid/ciaa1562

Clin Infect Dis 2021 Nov; 73(9): e3398-e3408

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.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.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.TruCulture offers a next-generation solution for whole-blood stimulation and immunomonitoring with the possibility to discriminate active and latent infection.