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Original Research: TUBERCULOSIS |

Tuberculin Skin Test and In Vitro Assays Provide Complementary Measures of Antimycobacterial Immunity in Children and Adolescents

Caroline J. Gallant, PhD; Aurelie Cobat, MD; Leah Simkin, MSc; Gillian F. Black, PhD; Kim Stanley, MSc; Jane Hughes, MSc; T. Mark Doherty, PhD; Willem A. Hanekom, MD; Brian Eley, MD; Nulda Beyers, MD; Jean-Philippe Jaïs, PhD; Paul van Helden, PhD; Laurent Abel, MD, PhD; Alexandre Alcaïs, MD, PhD; Eileen G. Hoal, PhD; Erwin Schurr, PhD
Author and Funding Information

From the McGill Centre for the Study of Host Resistance and Departments of Human Genetics and Medicine (Drs Gallant and Schurr, and Ms Simkin), McGill University, Montreal, QC, Canada; the Laboratory of Human Genetics of Infectious Diseases (Drs Cobat, Abel, and Alcaïs), Necker Branch, Institut National de la Santé et de la Recherche Médicale; the Université de Paris Descartes (Drs Cobat, Jaïs, Abel, and Alcaïs), Faculté de Médecine Necker, Paris, France; Molecular Biology and Human Genetics (Drs Black, van Helden, and Hoal; and Ms Stanley), MRC Centre for Molecular and Cellular Biology, DST/NRF Centre of Excellence for Biomedical TB Research, Faculty of Health Sciences, and the Desmond Tutu TB Centre (Dr Beyers), Department of Paediatrics and Child Health, Faculty of Health Sciences, Stellenbosch University, Tygerberg; the South African Tuberculosis Vaccine Initiative (Ms Hughes and Dr Hanekom), School of Child and Adolescent Health and Institute of Infectious Diseases and Molecular Medicine, Health Sciences Faculty, and the Paediatric Infectious Diseases Unit (Dr Eley), Red Cross Children’s Hospital, School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa; the Statens Serum Institute (Dr Doherty), Copenhagen, Denmark; and the Laboratory of Human Genetics of Infectious Diseases (Dr Abel), Rockefeller Branch, The Rockefeller University, New York, NY.

Correspondence to: Erwin Schurr, PhD, Montreal General Hospital Research Institute, 1650 Cedar Ave, Room L11-521, Montreal, QC, H3G 1A4, Canada; e-mail: erwin.schurr@mcgill.ca


Drs Gallant and Cobat contributed equally to the success of this study. Drs Hoal and Schurr share senior authorship.

Funding/Support: This study was supported by grants from the Sequella/Aeras Global Tuberculosis Foundation and the Canadian Institutes of Health Research (CIHR) to Dr Schurr. Dr Gallant is the recipient of a fellowship from the CIHR Strategic Training Centre in the Integrative Biology of Infectious Diseases and Autoimmunity. Dr Abel and Dr Alcaïs are supported by the Assistance Publique-Hopitaux de Paris, Programme de Recherche Fondamentale en Microbiologie, Maladies Infectieuses et Parasitaires, and the Agence Nationale de la Recherche of the Ministère Francais de l’Education Nationale de la Recherche et de la Technologie. Dr Schurr is a Chercheur National of the Fonds de recherche en santé du Québec and an International Research Scholar of the Howard Hughes Medical Institute.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestpubs.org/site/misc/reprints.xhtml).


© 2010 American College of Chest Physicians


Chest. 2010;137(5):1071-1077. doi:10.1378/chest.09-1852
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Background:  Although many studies have compared in vitro TB diagnostic tests with the venerable tuberculin skin test (TST), there is little understanding of the quantitative relationship between critical measures of antimycobacterial immunity used to detect TB infection. We, therefore, decided to determine the degree of redundancy between quantitative read-outs of in vivo and in vitro assays of antimycobacterial immunity.

Methods:  We enrolled 475 healthy HIV-negative children and young adults living in a hyperendemic area of TB. We measured in vivo TST responses, and a 1:10 diluted 3- or 7-day whole-blood assay was used to determine the in vitro antigen-specific interferon (IFN)-γ cytokine release. The frequency of antigen-specific IFN-γ+CD4+ and IFN-γ+CD8+ cells was tested using intracellular cytokine staining after 1 day incubation.

Results:  In vivo TST responses segregated into two well-separated groups with either no measurable response (TST induration < 5 mm; n = 164) or a normally distributed group with TST indurations ≥ 5 mm with peak at 15 mm (n = 260). In vitro assays provided a less pronounced separation of responders and nonresponders. Correlation analysis of responses among persons with TST ≥ 5 mm demonstrated that extent of TST response was poorly correlated with IFN-γ release (coefficients of correlation ρ = 0.17-0.22) and frequency of IFN-γ+CD4+/CD8+ cells (ρ = 0.05-0.17) across three stimulating antigens (Mycobacterium bovis bacillus Calmette-Guérin, purified protein derivative, early-secreted antigenic target-6).

Conclusion:  We conclude that in vivo and in vitro assays are nonredundant, complementary measures of antimycobacterial immunity. Both TST and in vitro assays provided valuable information about antimycobacterial immunity and by inference latent TB in the studied high-incidence TB settings.

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