CD38+CD27-TNF-α+on Mtb-specific CD4+T Cells Is a Robust Biomarker for Tuberculosis Diagnosis

Acharya, MP and Pradeep, SP and Murthi, VS and Chikkannaiah, P and Kambar, V and Narayanashetty, S and Burugina Nagaraja, S and Gangadhar, N and Yoganand, R and Satchidanandam, V (2021) CD38+CD27-TNF-α+on Mtb-specific CD4+T Cells Is a Robust Biomarker for Tuberculosis Diagnosis. In: Clinical Infectious Diseases, 73 (5). pp. 793-801.

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Abstract

Background: Early and accurate diagnosis followed by timely treatment are the key prerequisites to fight tuberculosis (TB) and reduce its global burden. Despite scientific advances, the rapid and correct diagnosis of both pulmonary and extrapulmonary tuberculosis remains a challenge because of traditional reliance on detection of the elusive bacilli. Mycobacterium tuberculosis (Mtb)-specific host immune activation and cytokine production have shown significant promise as alternative means of detecting and distinguishing active disease from latent infection. We queried the diagnostic ability of phenotypic markers on Mtb-specific cytokine-producing immune cell subsets for identifying active TB. Methods: Subjects belonging to the following groups were recruited: pulmonary and extrapulmonary TB, latent TB, cured TB, sick controls, and healthy controls. Polychromatic flow cytometry was used to identify host immune biomarkers in an exploratory cohort comprising 56 subjects using peripheral blood mononuclear cells. Clinical performance of the identified biomarker was evaluated using whole blood in a blinded validation cohort comprising 165 individuals. Results: Cytokine secreting frequencies of Mtb-specific cluster of differentiation 4-positive (CD4+) T cells with CD38+CD27- phenotype clearly distinguished infected individuals with active tuberculosis from those without disease. Tumor necrosis factor-α (TNF-α) secretion from CD38+CD27-CD4+ T cells upon stimulation with ESAT6/CFP10 peptides had the best diagnostic accuracy at a cutoff of 9.91 (exploratory: 96.67 specificity, 88.46 sensitivity; validation: 96.15 specificity, 90.16 sensitivity). Additionally, this subset differentiated treatment-naive patients with TB from individuals cured of TB following completion of anti-TB therapy. Conclusions: Mtb-specific CD38+CD27-TNF-α+CD4+ T-cell subset is a robust biomarker both for diagnosing TB and assessing cure. © 2021 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America.

Item Type:	Journal Article
Publication:	Clinical Infectious Diseases
Publisher:	Oxford University Press
Additional Information:	The copyright for this article belongs to Oxford University Press.
Keywords:	ADP ribosyl cyclase/cyclic ADP ribose hydrolase 1; culture filtrate protein 10; early secretory antigenic target 6; tumor necrosis factor; bacterial antigen; biological marker; tumor necrosis factor, adolescent; adult; aged; Article; CD4+ T lymphocyte; cohort analysis; controlled study; cytokine release; diagnostic accuracy; diagnostic test accuracy study; extrapulmonary tuberculosis; female; flow cytometry; human; human cell; latent tuberculosis; lung tuberculosis; lymphocyte activation; lymphocyte differentiation; major clinical study; male; middle aged; Mycobacterium tuberculosis; peripheral blood mononuclear cell; phenotype; sensitivity and specificity; validation process; young adult; CD4+ T lymphocyte; mononuclear cell; Mycobacterium tuberculosis; tuberculosis, Antigens, Bacterial; Biomarkers; CD4-Positive T-Lymphocytes; Humans; Latent Tuberculosis; Leukocytes, Mononuclear; Mycobacterium tuberculosis; Tuberculosis; Tumor Necrosis Factor-alpha
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	24 Feb 2023 04:11
Last Modified:	24 Feb 2023 04:11
URI:	https://eprints.iisc.ac.in/id/eprint/80401

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