Immune Profiling Enables Stratification of Patients With Active Tuberculosis Disease or Mycobacteriu
m tuberculosis Infection
Author:
Duffy Darragh12ORCID, Nemes Elisa3, Llibre Alba12, Rouilly Vincent4, Musvosvi Munyaradzi3, Smith Nikaïa12, Filander Elizabeth3, Africa Hadn3, Mabwe Simbarashe3, Jaxa Lungisa3, Charbit Bruno5, Mulenga Humphrey3, Tameris Michele3, Walzl Gerhard6, Malherbe Stephanus6, Thomas Stephanie12, Hatherill Mark3, Bilek Nicole3, Scriba Thomas J3, Albert Matthew L7, Abel Laurent, Alcover Andres, Aschard Hugues, Astrom Kalla, Bousso Philippe, Bruhns Pierre, Cumano Ana, Demangel Caroline, Deriano Ludovic, Di Santo James, Dromer Françoise, Eberl Gérard, Enninga Jost, Fellay Jacques, Gelpi Odile, Gomperts-Boneca Ivo, Hasan Milena, Hercberg Serge, Lantz Olivier, Leclerc Claude, Mouquet Hugo, Patin Etienne, Pellegrini Sandra, Pol Stanislas, Rausell Antonio, Rogge Lars, Sakuntabhai Anavaj, Schwartz Olivier, Schwikowski Benno, Shorte Spencer, Soumelis Vassili, Tangy Frédéric, Tartour Eric, Toubert Antoine, Touvier Mathilde, Ungeheuer Marie-Noëlle, L. Albert Matthew, Duffy Darragh, Quintana-Murci Lluis,
Affiliation:
1. Immunobiology of Dendritic Cells, Institut Pasteur, Paris, France 2. Inserm U1223, Institut Pasteur, Paris, France 3. South African Tuberculosis Vaccine Initiative (SATVI), Division of Immunology, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa 4. DATACTIX, Paris, France 5. Centre for Translational Research, Institut Pasteur, Paris, France 6. Department of Science and Technology-National Research Foundation (DST-NRF) Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa 7. Insitro, San Francisco, California, USA
Abstract
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 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.
Funder
Bill and Melinda Gates Foundation French Government’s Investissement d’Avenir Program Laboratoire d’Excellence “Milieu Intérieur”
Publisher
Oxford University Press (OUP)
Subject
Infectious Diseases,Microbiology (medical)
Cited by
17 articles.
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