PMID- 34492697
OWN - NLM
STAT- MEDLINE
DCOM- 20210922
LR  - 20211012
IS  - 1537-6591 (Electronic)
IS  - 1058-4838 (Linking)
VI  - 73
IP  - 5
DP  - 2021 Sep 7
TI  - CD38+CD27-TNF-alpha + on Mtb-specific CD4+ T Cells Is a Robust Biomarker for 
      Tuberculosis Diagnosis.
PG  - 793-801
LID - 10.1093/cid/ciab144 [doi]
AB  - 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-alpha (TNF-alpha) 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-alpha +CD4+ 
      T-cell subset is a robust biomarker both for diagnosing TB and assessing cure.
CI  - (c) The Author(s) 2021. Published by Oxford University Press for the Infectious 
      Diseases Society of America. All rights reserved. For permissions, e-mail: 
      journals.permissions@oup.com.
FAU - Acharya, Muthya Pragun
AU  - Acharya MP
AD  - Department of Microbiology and Cell Biology, Indian Institute of Science, 
      Bengaluru, India.
FAU - Pradeep, Sai Pallavi
AU  - Pradeep SP
AD  - Department of Microbiology and Cell Biology, Indian Institute of Science, 
      Bengaluru, India.
FAU - Murthy, Venkataramappa Srinivasa
AU  - Murthy VS
AD  - Department of Pathology, Employees State Insurance Corporation Medical College & 
      Post Graduate Institute of Medical Sciences & Research (ESIC MC & PGIMSR), 
      Bengaluru, India.
FAU - Chikkannaiah, Panduranga
AU  - Chikkannaiah P
AD  - Department of Pathology, Employees State Insurance Corporation Medical College & 
      Post Graduate Institute of Medical Sciences & Research (ESIC MC & PGIMSR), 
      Bengaluru, India.
FAU - Kambar, Vivekanand
AU  - Kambar V
AD  - Department of Pulmonology, ESIC MC & PGIMSR, Bengaluru, India.
FAU - Narayanashetty, Satyanarayana
AU  - Narayanashetty S
AD  - Department of General Medicine, ESIC MC & PGIMSR, Bengaluru, India.
FAU - Burugina Nagaraja, Sharath
AU  - Burugina Nagaraja S
AD  - Department of Community Medicine, ESIC MC & PGIMSR, Bengaluru, India.
FAU - Gangadhar, Niveditha
AU  - Gangadhar N
AD  - Department of Pharmacology, ESIC MC & PGIMSR, Bengaluru, India.
FAU - Yoganand, Raksha
AU  - Yoganand R
AD  - Department of Microbiology, ESIC MC & PGIMSR, Bengaluru, India.
FAU - Satchidanandam, Vijaya
AU  - Satchidanandam V
AUID- ORCID: 0000-0003-3276-6572
AD  - Department of Microbiology and Cell Biology, Indian Institute of Science, 
      Bengaluru, India.
LA  - eng
GR  - BT/PR27952/INF/22/212/2018/Department of Biotechnology, Government of India/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Infect Dis
JT  - Clinical infectious diseases : an official publication of the Infectious Diseases 
      Society of America
JID - 9203213
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Biomarkers)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Antigens, Bacterial
MH  - Biomarkers
MH  - CD4-Positive T-Lymphocytes
MH  - Humans
MH  - *Latent Tuberculosis/diagnosis
MH  - Leukocytes, Mononuclear
MH  - *Mycobacterium tuberculosis
MH  - *Tuberculosis
MH  - Tumor Necrosis Factor-alpha
OTO - NOTNLM
OT  - TNF-alpha
OT  - biomarker
OT  - diagnosis
OT  - flow cytometry
OT  - tuberculosis
EDAT- 2021/09/08 06:00
MHDA- 2021/09/23 06:00
CRDT- 2021/09/07 20:28
PHST- 2020/10/05 00:00 [received]
PHST- 2021/09/07 20:28 [entrez]
PHST- 2021/09/08 06:00 [pubmed]
PHST- 2021/09/23 06:00 [medline]
AID - 6144985 [pii]
AID - 10.1093/cid/ciab144 [doi]
PST - ppublish
SO  - Clin Infect Dis. 2021 Sep 7;73(5):793-801. doi: 10.1093/cid/ciab144.