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

SUBMITTER: Duffy D 

PROVIDER: S-EPMC8563210 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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

Duffy Darragh D   Nemes Elisa E   Llibre Alba A   Rouilly Vincent V   Musvosvi Munyaradzi M   Smith Nikaïa N   Filander Elizabeth E   Africa Hadn H   Mabwe Simbarashe S   Jaxa Lungisa L   Charbit Bruno B   Mulenga Humphrey H   Tameris Michele M   Walzl Gerhard G   Malherbe Stephanus S   Thomas Stephanie S   Hatherill Mark M   Bilek Nicole N   Scriba Thomas J TJ   Albert Matthew L ML  

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20211101 9


<h4>Background</h4>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.<h4>Methods</h4>We hypothesized that TruCulture, an immunomonitoring method for whole-blood stimulation, could discriminate active disease from latent Mtb infection (LT  ...[more]

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