Immunity & infection

Oral

Ifn-γ-based Stratification of Latent Infection and Active Tuberculosis Disease Using a Novel Whole Blood Stimulation System

Wednesday, June 14
6:15 PM - 7:45 PM

Tuberculosis (TB) is a global public health crisis with an estimated 1.7 billion latently infected individuals worldwide.An effective blood based biomarker test to diagnose patients with active TB disease is urgently needed. Current diagnosis depends on detection of bacteria by microscopy, culture or PCR in sputum. We tested the capacity of TruCulture, a novel whole blood collection and stimulation system, to stratify patients with active disease from latently infected individuals. Using Mycobacterium tuberculosis (M.tb) antigens, we stimulated whole blood from 25 active TB and 25 latently infected individuals. Supernatants were assessed by Luminex multi-analyte profiling and ultrasensitive digital Simoa ELISA, and RNA by Nanostring gene expression arrays. Utilizing M.tb antigen-induced IFN-γ as a diagnostic readout ROC curve analysis showed a better stratification of diseased from latently infected individuals using TruCulture (AUC=0.814) as compared to QuantiFERON-TB Gold (AUC=0.558). TruCulture resulted in significantly lower background IFN-γ secretion, which we interpreted as the reason for improved signal detection of antigen-specific responses. Utilizing Simoa (limit of detection = 11fg/ml) the majority of latently infected donors secreted less than 14 pg/ml of IFN-γ (QuantiFERON cutoff) following TruCulture M.tb antigen stimulation. Interestingly, hierarchical clustering analysis of gene expression data identified a subset of latently infected donors with high IFN-γ expression. Current investigations are examining whether this signature is indicative of near-term conversion to active disease. In sum, our study demonstrates the enhanced specificity of TruCulture versus the current gold-standard QuantiFERON test for diagnosis of active TB in areas where latent infection is highly prevalent.

Alba Llibre

Institut Pasteur

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    Elisa Nemes

    South African Tuberculosis Vaccine Initiative (SATVI), Division of Immunology, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, University of Cape Town

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      Vincent Rouilly

      Institut Pasteur

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        Celine Posseme

        Institut Pasteur

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          Simba Mabwe

          South African Tuberculosis Vaccine Initiative (SATVI), Division of Immunology, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, University of Cape Town

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            Humphrey Mulenga

            South African Tuberculosis Vaccine Initiative (SATVI), Division of Immunology, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, University of Cape Town

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              Munyaradzi Musvosvi

              South African Tuberculosis Vaccine Initiative (SATVI), Division of Immunology, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, University of Cape Town

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                Stephanie Thomas

                Institut Pasteur

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                  Nicole Bilek

                  South African Tuberculosis Vaccine Initiative (SATVI), Division of Immunology, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, University of Cape Town

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                    Thomas J. Scriba

                    South African Tuberculosis Vaccine Initiative (SATVI), Division of Immunology, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, University of Cape Town

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                      Matthew Albert

                      Institut Pasteur

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                        Darragh Duffy

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                          Ifn-γ-based Stratification of Latent Infection and Active Tuberculosis Disease Using a Novel Whole Blood Stimulation System



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