Defining the role of cellular immune signatures in diagnostic evaluation of suspected tuberculosis

Alice Halliday, Tereza Masonou, Mica R Tolosa-Wright, Yanping Guo, Long Hoang, Robert Parker, Aime A Boakye , Yemisi Takwoingi, Amarjit Badhan, Pooja Jain, Ishita Marwah, Luis C. Berrocal-Almanza, Jon Deeks, Peter Beverley, Onn Min Kon, Ajit Lalvani

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Abstract

Background: Diagnosis of paucibacillary tuberculosis (TB) including extrapulmonary TB is a significant challenge, particularly in high-income, low-incidence settings. Measurement of Mycobacterium tuberculosis (Mtb)-specific cellular immune signatures by flow cytometry discriminates active TB from latent TB infection (LTBI) in case-control studies; however, their diagnostic accuracy and clinical utility in routine clinical practice is unknown.

Methods: Using a nested case-control study design within a prospective multicenter cohort of patients presenting with suspected TB in England, we assessed diagnostic accuracy of signatures in 134 patients who tested interferon-gamma release assay (IGRA)-positive and had final diagnoses of TB or non-TB diseases with coincident LTBI. Cellular signatures were measured using flow cytometry.

Results: All signatures performed less well than previously reported. Only signatures incorporating measurement of phenotypic markers on functional Mtb-specific CD4 T cells discriminated active TB from non-TB diseases with LTBI. The signatures measuring HLA-DR+IFNγ + CD4 T cells and CD45RA−CCR7−CD127− IFNγ −IL-2−TNFα + CD4 T cells performed best with 95% positive predictive value (95% confidence interval, 90–97) in the clinically challenging subpopulation of IGRA-positive but acid-fast bacillus (AFB) smear-negative TB suspects.

Conclusions: Two cellular immune signatures could improve and accelerate diagnosis in the challenging group of patients who are IGRA-positive, AFB smear-negative, and have paucibacillary TB.
Original languageEnglish
Pages (from-to)1632–1641
Number of pages10
JournalThe Journal of Infectious Diseases
Volume225
Issue number9
Early online date31 Jul 2021
DOIs
Publication statusPublished - 1 May 2022

Keywords

  • T cell
  • diagnostic
  • flow cytometry
  • latent tuberculosis infection
  • tuberculosis

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