Ontology highlight
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
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]