Journal Article

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

Molebogeng X. Rangaka, Lavanya Diwakar, Ronnett Seldon, Gilles van Cutsem, Graeme A. Meintjes, Chelsea Morroni, Priscilla Mouton, Muki S. Shey, Gary Maartens, Katalin A. Wilkinson and Robert J. Wilkinson

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 44, issue 12, pages 1639-1646
Published in print June 2007 | ISSN: 1058-4838
Published online June 2007 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/518234
Clinical, Immunological, and Epidemiological Importance of Antituberculosis T Cell Responses in HIV-Infected Africans

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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 (P < .001). 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 (P ⩽ .04), 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.

Journal Article.  5193 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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