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

Autor: Robert Parker, Jonathan J Deeks, Tereza Masonou, Onn Min Kon, Long Hoang, Pooja Jain, Yanping Guo, Amarjit Badhan, Luis C Berrocal-Almanza, Yemisi Takwoingi, Alice Halliday, Peter Beverley, Aime Boakye, Ajit Lalvani, Mica Tolosa-Wright, Ishita Marwah
Přispěvatelé: National Institute for Health Research
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Tuberculosis
T cell
latent tuberculosis infection
Immunology
diagnostic
Diagnostic evaluation
Microbiology
Flow cytometry
Mycobacterium tuberculosis
03 medical and health sciences
0302 clinical medicine
Immune system
Latent Tuberculosis
Immunology and Allergy
Medicine
TOOL
Humans
030212 general & internal medicine
Prospective Studies
Medical diagnosis
11 Medical and Health Sciences
Science & Technology
biology
medicine.diagnostic_test
business.industry
flow cytometry
ACTIVE TUBERCULOSIS
06 Biological Sciences
biology.organism_classification
medicine.disease
030104 developmental biology
medicine.anatomical_structure
Infectious Diseases
tuberculosis
Case-Control Studies
Cohort
MYCOBACTERIUM-TUBERCULOSIS
business
Life Sciences & Biomedicine
Interferon-gamma Release Tests
RESPONSES
Zdroj: Halliday, A, Masonou, T, Tolosa-Wright, M R, Guo, Y, Hoang, L, Parker, R, Boakye, A, Takwoingi, Y, Badhan, A, Jain, P, Marwah, I, Berrocal-Almanza, L C, Deeks, J J, Beverley, P, Kon, O M & Lalvani, A 2021, ' Defining the role of cellular immune signatures in diagnostic evaluation of suspected tuberculosis ', Journal of Infectious Diseases . https://doi.org/10.1093/infdis/jiab311
Popis: 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.
Databáze: OpenAIRE