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Corrigendum Free access | 10.1172/JCI83279

Biomarkers on patient T cells diagnose active tuberculosis and monitor treatment response

Toidi Adekambi,1 Chris C. Ibegbu,1 Stephanie Cagle,2 Ameeta S. Kalokhe,1,2 Yun F. Wang,3,4 Yijuan Hu,5 Cheryl L. Day,1,6,7 Susan M. Ray,2 and Jyothi Rengarajan1,2

1Emory Vaccine Center and

2Division of Infectious Disease, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.

3Department of Pathology, Grady Memorial Hospital, Atlanta, Georgia, USA.

4Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.

5Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, Georgia, USA.

6Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.

7South African Tuberculosis Vaccine Initiative (SATVI) and School of Child and Adolescent Health, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory, South Africa.

Find articles by Adekambi, T. in: JCI | PubMed | Google Scholar

1Emory Vaccine Center and

2Division of Infectious Disease, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.

3Department of Pathology, Grady Memorial Hospital, Atlanta, Georgia, USA.

4Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.

5Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, Georgia, USA.

6Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.

7South African Tuberculosis Vaccine Initiative (SATVI) and School of Child and Adolescent Health, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory, South Africa.

Find articles by Ibegbu, C. in: JCI | PubMed | Google Scholar

1Emory Vaccine Center and

2Division of Infectious Disease, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.

3Department of Pathology, Grady Memorial Hospital, Atlanta, Georgia, USA.

4Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.

5Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, Georgia, USA.

6Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.

7South African Tuberculosis Vaccine Initiative (SATVI) and School of Child and Adolescent Health, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory, South Africa.

Find articles by Cagle, S. in: JCI | PubMed | Google Scholar

1Emory Vaccine Center and

2Division of Infectious Disease, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.

3Department of Pathology, Grady Memorial Hospital, Atlanta, Georgia, USA.

4Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.

5Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, Georgia, USA.

6Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.

7South African Tuberculosis Vaccine Initiative (SATVI) and School of Child and Adolescent Health, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory, South Africa.

Find articles by Kalokhe, A. in: JCI | PubMed | Google Scholar

1Emory Vaccine Center and

2Division of Infectious Disease, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.

3Department of Pathology, Grady Memorial Hospital, Atlanta, Georgia, USA.

4Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.

5Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, Georgia, USA.

6Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.

7South African Tuberculosis Vaccine Initiative (SATVI) and School of Child and Adolescent Health, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory, South Africa.

Find articles by Wang, Y. in: JCI | PubMed | Google Scholar

1Emory Vaccine Center and

2Division of Infectious Disease, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.

3Department of Pathology, Grady Memorial Hospital, Atlanta, Georgia, USA.

4Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.

5Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, Georgia, USA.

6Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.

7South African Tuberculosis Vaccine Initiative (SATVI) and School of Child and Adolescent Health, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory, South Africa.

Find articles by Hu, Y. in: JCI | PubMed | Google Scholar

1Emory Vaccine Center and

2Division of Infectious Disease, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.

3Department of Pathology, Grady Memorial Hospital, Atlanta, Georgia, USA.

4Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.

5Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, Georgia, USA.

6Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.

7South African Tuberculosis Vaccine Initiative (SATVI) and School of Child and Adolescent Health, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory, South Africa.

Find articles by Day, C. in: JCI | PubMed | Google Scholar

1Emory Vaccine Center and

2Division of Infectious Disease, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.

3Department of Pathology, Grady Memorial Hospital, Atlanta, Georgia, USA.

4Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.

5Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, Georgia, USA.

6Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.

7South African Tuberculosis Vaccine Initiative (SATVI) and School of Child and Adolescent Health, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory, South Africa.

Find articles by Ray, S. in: JCI | PubMed | Google Scholar

1Emory Vaccine Center and

2Division of Infectious Disease, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.

3Department of Pathology, Grady Memorial Hospital, Atlanta, Georgia, USA.

4Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.

5Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, Georgia, USA.

6Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.

7South African Tuberculosis Vaccine Initiative (SATVI) and School of Child and Adolescent Health, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory, South Africa.

Find articles by Rengarajan, J. in: JCI | PubMed | Google Scholar

First published September 1, 2015 - More info

Published in Volume 125, Issue 9 on September 1, 2015
J Clin Invest. 2015;125(9):3723–3723. https://doi.org/10.1172/JCI83279.
Copyright © 2015, American Society for Clinical Investigation
First published September 1, 2015 - Version history

Related article:

Biomarkers on patient T cells diagnose active tuberculosis and monitor treatment response
Toidi Adekambi, … , Susan M. Ray, Jyothi Rengarajan
Toidi Adekambi, … , Susan M. Ray, Jyothi Rengarajan
Clinical Medicine Immunology Infectious disease Microbiology

Biomarkers on patient T cells diagnose active tuberculosis and monitor treatment response

Abstract

BACKGROUND. The identification and treatment of individuals with tuberculosis (TB) is a global public health priority. Accurate diagnosis of pulmonary active TB (ATB) disease remains challenging and relies on extensive medical evaluation and detection of Mycobacterium tuberculosis (Mtb) in the patient’s sputum. Further, the response to treatment is monitored by sputum culture conversion, which takes several weeks for results. Here, we sought to identify blood-based host biomarkers associated with ATB and hypothesized that immune activation markers on Mtb-specific CD4+ T cells would be associated with Mtb load in vivo and could thus provide a gauge of Mtb infection.

METHODS. Using polychromatic flow cytometry, we evaluated the expression of immune activation markers on Mtb-specific CD4+ T cells from individuals with asymptomatic latent Mtb infection (LTBI) and ATB as well as from ATB patients undergoing anti-TB treatment.

RESULTS. Frequencies of Mtb-specific IFN-γ+CD4+ T cells that expressed immune activation markers CD38 and HLA-DR as well as intracellular proliferation marker Ki-67 were substantially higher in subjects with ATB compared with those with LTBI. These markers accurately classified ATB and LTBI status, with cutoff values of 18%, 60%, and 5% for CD38+IFN-γ+, HLA-DR+IFN-γ+, and Ki-67+IFN-γ+, respectively, with 100% specificity and greater than 96% sensitivity. These markers also distinguished individuals with untreated ATB from those who had successfully completed anti-TB treatment and correlated with decreasing mycobacterial loads during treatment.

CONCLUSION. We have identified host blood-based biomarkers on Mtb-specific CD4+ T cells that discriminate between ATB and LTBI and provide a set of tools for monitoring treatment response and cure.

TRIAL REGISTRATION. Registration is not required for observational studies.

FUNDING. This study was funded by Emory University, the NIH, and the Yerkes National Primate Center.

Authors

Toidi Adekambi, Chris C. Ibegbu, Stephanie Cagle, Ameeta S. Kalokhe, Yun F. Wang, Yijuan Hu, Cheryl L. Day, Susan M. Ray, Jyothi Rengarajan

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1Emory Vaccine Center and 2Division of Infectious Disease, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA. 3Department of Pathology, Grady Memorial Hospital, Atlanta, Georgia, USA. 4Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA. 5Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, Georgia, USA. 6Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA. 7South African Tuberculosis Vaccine Initiative (SATVI) and School of Child and Adolescent Health, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory, South Africa.

Original citation: J Clin Invest. 2015;125(5):1827–1838. doi:10.1172/JCI77990.

Citation for this corrigendum: J Clin Invest. 2015;125(9):3723. doi:10.1172/JCI83279.

Chris C. Ibegbu’s affiliation was incorrect. Cheryl L. Day’s third affiliation was omitted from the affiliations list. The correct author and affiliations lists are above. A sentence was omitted from the Acknowledgments. The correct sentence is below.

The authors also thank many additional members of the SATVI team who helped with enrollment and evaluation of participants.

The authors regret the errors.

Footnotes

See the related article beginning on page 1827.

Version history
  • Version 1 (September 1, 2015): No description
  • Version 2 (September 1, 2015): No description
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