Defining the role of cellular immune signatures in diagnostic evaluation of suspected tuberculosis
File(s)
Published version
Author(s)
Type
Journal Article
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.
Date Issued
2022-05-01
Date Acceptance
2021-06-14
Citation
Journal of Infectious Diseases, 2022, 225 (9), pp.1632-1641
ISSN
0022-1899
Publisher
Oxford University Press
Start Page
1632
End Page
1641
Journal / Book Title
Journal of Infectious Diseases
Volume
225
Issue
9
Copyright Statement
© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. F
Sponsor
National Institute for Health Research
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/34331451
PII: 6332782
Grant Number
12/65/27
Subjects
T cell
diagnostic
flow cytometry
latent tuberculosis infection
tuberculosis
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2021-07-31