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15 June 2007

Volume 44, Number 12
Clinical Infectious Diseases 2007;44:1639–1646
© 2007 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2007/4412-0018$15.00
DOI: 10.1086/518234
HIV/AIDS MAJOR ARTICLE

Clinical, Immunological, and Epidemiological Importance of Antituberculosis T Cell Responses in HIV‐Infected Africans

Molebogeng X. Rangaka,1,5,a

Lavanya Diwakar,1,a

Ronnett Seldon,1

Gilles van Cutsem,5

Graeme A. Meintjes,1,6

Chelsea Morroni,2

Priscilla Mouton,1,5

Muki S. Shey,1

Gary Maartens,1,3,4

Katalin A. Wilkinson,1,7,a and

Robert J. Wilkinson1,4,6,7

1Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, 2School of Public Health, 3Division of Pharmacology, and 4Department of Medicine, University of Cape Town, Cape Town, 5Medicins Sans Frontieres, Khayelitsha site B, Khayelitsha, and 6G.F. Jooste Hospital, Manenberg, South Africa; and 7Division of Medicine, Imperial College London, United Kingdom

Background.Human immunodeficiency virus (HIV)–associated tuberculosis is a major cause of mortality in Africa. The assay of T cell interferon‐γ released in response to antigens of greater specificity than purified protein derivative is a useful improvement over the Mantoux tuberculin skin test, but few studies have evaluated interferon‐γ secretion in HIV‐infected individuals.

Methods.Mycobacterium tuberculosis antigen–specific interferon‐γ secretion was assessed by whole blood assay and enzyme‐linked immunospot, which were compared with the Mantoux tuberculin skin test in HIV‐infected and HIV‐uninfected individuals without active tuberculosis and HIV‐infected patients with pulmonary tuberculosis in Khayelitsha, South Africa.

Results.The skin test and whole blood assay responses to purified protein derivative in HIV‐positive subjects were decreased, compared with responses in HIV‐negative subjects ( ). By contrast, the responses to M. tuberculosis antigens (early secreted antigenic target 6, culture filtrate protein 10, TB10.3, and α‐crystallin 2) were less affected, indicating a high prevalence of latent tuberculosis (80%) in both HIV‐negative and HIV‐positive subject groups. Whole blood assay responses did not differ between the HIV‐positive subjects without tuberculosis and HIV‐positive subjects with tuberculosis, but the enzyme‐linked immunospot method response to early secreted antigenic target 6 and culture filtrate protein 10 was higher in the group of HIV‐infected subjects with tuberculosis ( ), although this group had lower CD4+ cell counts. A ratio of the combined enzyme‐linked immunospot method response divided by the CD4+ cell count of >1.0 had 88% sensitivity and 80% specificity for active pulmonary tuberculosis in HIV‐infected individuals.

Conclusions.Interferon‐γ release appears to be less impaired than skin testing by HIV coinfection. The novel potential to relate the enzyme‐linked immunospot method and CD4+ cell count to assist diagnosis of active tuberculosis in patients with HIV infection is important and deserves further evaluation.

Received 25 November 2006; accepted 28 February 2007; electronically published 10 May 2007.

Reprints or correspondence: Dr. Robert J. Wilkinson, Rm. S2.19.4 Institute of Infectious Diseases and Molecular Medicine, Wernher and Beit Bldng. South, Faculty of Health Sciences, University of Cape Town, Anzio Rd., Observatory 7925, South Africa ().

Cited by

Mary-Ann Davies, Tom Connell, Christine Johannisen, Kathryn Wood, Sandy Pienaar, Katalin A Wilkinson, Robert J Wilkinson, Heather J Zar, Brian Eley, David Beatty, Nigel Curtis, Mark P Nicol. (2009) Detection of tuberculosis in HIV-infected children using an enzyme-linked immunospot assay. AIDS 23:8, 961-969
Online publication date: 1-Jun-2009.
CrossRef
Keertan Dheda, Richard van Zyl Smit, Motasim Badri, Madhukar Pai. (2009) T-cell interferon-γ release assays for the rapid immunodiagnosis of tuberculosis: clinical utility in high-burden vs. low-burden settings. Current Opinion in Pulmonary Medicine 15:3, 188-200
Online publication date: 1-Jun-2009.
CrossRef
Maximilian C. Aichelburg, Armin Rieger, Florian Breitenecker, Katharina Pfistershammer, Julia Tittes, Stephanie Eltz, Alexander C. Aichelburg, Georg Stingl, Athanasios Makristathis, and Norbert Kohrgruber. (2009) Detection and Prediction of Active Tuberculosis Disease by a Whole‐Blood Interferon‐γ Release Assay in HIV‐1–Infected Individuals. Clinical Infectious Diseases 48:7, 954-962
Online publication date: 1-Apr-2009.
Abstract-Full Text-PDF Version (366 kB)
Heike Sarrazin, Katalin Andrea Wilkinson, Jan Andersson, Molebogeng Xheeda Rangaka, Lena Radler, Kerryn van Veen, Christoph Lange, and Robert John Wilkinson. (2009) Association between Tuberculin Skin Test Reactivity, the Memory CD4 Cell Subset, and Circulating FoxP3‐Expressing Cells in HIV‐Infected Persons. The Journal of Infectious Diseases 199:5, 702-710
Online publication date: 1-Mar-2009.
Abstract-Full Text-PDF Version (277 kB)
Graeme Meintjes, Molebogeng X. Rangaka, Gary Maartens, Kevin Rebe, Chelsea Morroni, Dominique J. Pepper, Katalin A. Wilkinson, and Robert J. Wilkinson. (2009) Novel Relationship between Tuberculosis Immune Reconstitution Inflammatory Syndrome and Antitubercular Drug Resistance. Clinical Infectious Diseases 48:5, 667-676
Online publication date: 1-Mar-2009.
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Lingyun Shao, Wenhong Zhang, Shu Zhang, Crystal Y Chen, Weimin Jiang, Yunya Xu, Chengyan Meng, Xinhua Weng, Zheng W Chen. (2008) Potent immune responses of Ag-specific Vγ2Vδ2+ T cells and CD8+ T cells associated with latent stage of Mycobacterium tuberculosis coinfection in HIV-1-infected humans. AIDS 22:17, 2241-2250
Online publication date: 1-Dec-2008.
CrossRef
Peter Daley, Poorvi Chordia. (2008) What is the clinical utility of interferon-γ release assays for the diagnosis of TB in high-TB-burden countries?. Therapy 5:3, 367-375
Online publication date: 1-Jun-2008.
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Delia Goletti, Stefania Carrara, Donatella Vincenti, and Enrico Girardi. (2007) T Cell Responses to Commercial Mycobacterium tuberculosis–Specific Antigens in HIV‐Infected Patients. Clinical Infectious Diseases 45:12, 1652-1654
Online publication date: 15-Dec-2007.
Citation-Full Text-PDF Version (386 kB)

  • M.X.R., L.D., and K.A.W. contributed equally to this article.

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