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- Title
Defining the Role of Cellular Immune Signatures in Diagnostic Evaluation of Suspected Tuberculosis.
- Authors
Halliday, Alice; Masonou, Tereza; Tolosa-Wright, Mica R; Guo, Yanping; Hoang, Long; Parker, Robert; Boakye, Aime; Takwoingi, Yemisi; Badhan, Amarjit; Jain, Pooja; Marwah, Ishita; Berrocal-Almanza, Luis C; Deeks, Jonathan; Beverley, Peter; Kon, Onn Min; Lalvani, Ajit
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
ENGLAND; LATENT tuberculosis; INTERFERON gamma release tests; LATENT infection; MYCOBACTERIUM tuberculosis; CONTACT tracing; TUBERCULOSIS; TUBERCULOUS meningitis; TUBERCULOSIS diagnosis; RESEARCH; RESEARCH methodology; CASE-control method; EVALUATION research; COMPARATIVE studies; RESEARCH funding; LONGITUDINAL method
- Publication
Journal of Infectious Diseases, 2022, Vol 225, Issue 9, p1632
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiab311