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

Research output: Contribution to journalArticlepeer-review

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Defining the role of cellular immune signatures in diagnostic evaluation of suspected tuberculosis. / Halliday, Alice ; Masonou, Tereza ; Tolosa-Wright, Mica R ; Guo, Yanping ; Hoang, Long ; Parker, Robert ; Boakye , Aime A ; Takwoingi, Yemisi; Badhan, Amarjit ; Jain, Pooja ; Marwah, Ishita; Berrocal-Almanza, Luis C. ; Deeks, Jon; Beverley, Peter; Kon, Onn Min; Lalvani, Ajit.

In: The Journal of Infectious Diseases, 14.06.2021.

Research output: Contribution to journalArticlepeer-review

Harvard

Halliday, A, Masonou, T, Tolosa-Wright, MR, Guo, Y, Hoang, L, Parker, R, Boakye , AA, Takwoingi, Y, Badhan, A, Jain, P, Marwah, I, Berrocal-Almanza, LC, Deeks, J, Beverley, P, Kon, OM & Lalvani, A 2021, 'Defining the role of cellular immune signatures in diagnostic evaluation of suspected tuberculosis', The Journal of Infectious Diseases. https://doi.org/10.1093/infdis/jiab311

APA

Halliday, A., Masonou, T., Tolosa-Wright, M. R., Guo, Y., Hoang, L., Parker, R., Boakye , A. A., Takwoingi, Y., Badhan, A., Jain, P., Marwah, I., Berrocal-Almanza, L. C., Deeks, J., Beverley, P., Kon, O. M., & Lalvani, A. (Accepted/In press). Defining the role of cellular immune signatures in diagnostic evaluation of suspected tuberculosis. The Journal of Infectious Diseases. https://doi.org/10.1093/infdis/jiab311

Vancouver

Author

Halliday, Alice ; Masonou, Tereza ; Tolosa-Wright, Mica R ; Guo, Yanping ; Hoang, Long ; Parker, Robert ; Boakye , Aime A ; Takwoingi, Yemisi ; Badhan, Amarjit ; Jain, Pooja ; Marwah, Ishita ; Berrocal-Almanza, Luis C. ; Deeks, Jon ; Beverley, Peter ; Kon, Onn Min ; Lalvani, Ajit. / Defining the role of cellular immune signatures in diagnostic evaluation of suspected tuberculosis. In: The Journal of Infectious Diseases. 2021.

Bibtex

@article{355659526bab4d49bcadfdbc30fd155d,
title = "Defining the role of cellular immune signatures in diagnostic evaluation of suspected tuberculosis",
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.",
keywords = "diagnostic, flow cytometry, latent tuberculosis infection, T cell, tuberculosis",
author = "Alice Halliday and Tereza Masonou and Tolosa-Wright, {Mica R} and Yanping Guo and Long Hoang and Robert Parker and Boakye, {Aime A} and Yemisi Takwoingi and Amarjit Badhan and Pooja Jain and Ishita Marwah and Berrocal-Almanza, {Luis C.} and Jon Deeks and Peter Beverley and Kon, {Onn Min} and Ajit Lalvani",
note = "Final Version of Record not yet available as of 14/10/2021.",
year = "2021",
month = jun,
day = "14",
doi = "10.1093/infdis/jiab311",
language = "English",
journal = "The Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",

}

RIS

TY - JOUR

T1 - Defining the role of cellular immune signatures in diagnostic evaluation of suspected tuberculosis

AU - Halliday, Alice

AU - Masonou, Tereza

AU - Tolosa-Wright, Mica R

AU - Guo, Yanping

AU - Hoang, Long

AU - Parker, Robert

AU - Boakye , Aime A

AU - Takwoingi, Yemisi

AU - Badhan, Amarjit

AU - Jain, Pooja

AU - Marwah, Ishita

AU - Berrocal-Almanza, Luis C.

AU - Deeks, Jon

AU - Beverley, Peter

AU - Kon, Onn Min

AU - Lalvani, Ajit

N1 - Final Version of Record not yet available as of 14/10/2021.

PY - 2021/6/14

Y1 - 2021/6/14

N2 - 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.

AB - 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.

KW - diagnostic

KW - flow cytometry

KW - latent tuberculosis infection

KW - T cell

KW - tuberculosis

U2 - 10.1093/infdis/jiab311

DO - 10.1093/infdis/jiab311

M3 - Article

JO - The Journal of Infectious Diseases

JF - The Journal of Infectious Diseases

SN - 0022-1899

ER -