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- Title
Immune Profiling Enables Stratification of Patients With Active Tuberculosis Disease or Mycobacterium tuberculosis Infection.
- Authors
Duffy, Darragh; Nemes, Elisa; Llibre, Alba; Rouilly, Vincent; Musvosvi, Munyaradzi; Smith, Nikaïa; Filander, Elizabeth; Africa, Hadn; Mabwe, Simbarashe; Jaxa, Lungisa; Charbit, Bruno; Mulenga, Humphrey; Tameris, Michele; Walzl, Gerhard; Malherbe, Stephanus; Thomas, Stephanie; Hatherill, Mark; Bilek, Nicole; Scriba, Thomas J; Albert, Matthew L
- 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.
- Subjects
MYCOBACTERIAL disease diagnosis; ANTIGEN analysis; BLOOD testing; PROTEIN analysis; TUBERCULOSIS diagnosis; INTERFERON gamma release tests; CYTOKINES; BIOMARKERS; PREDICTIVE tests; BACILLUS (Bacteria); IMMUNOPHENOTYPING; ENZYME-linked immunosorbent assay
- Publication
Clinical Infectious Diseases, 2021, Vol 73, Issue 9, pe3398
- ISSN
1058-4838
- Publication type
Article
- DOI
10.1093/cid/ciaa1562