Clinical, immunological, and epidemiological importance of antituberculosis T cell responses in HIV-infected Africans.

Abstract

BACKGROUND:

Human immunodeficiency virus (HIV)-associated tuberculosis is a major cause of mortality in Africa. The assay of T cell interferon- gamma 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-gamma secretion in HIV-infected individuals.

METHODS:

Mycobacterium tuberculosis antigen-specific interferon-gamma 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 alpha-crystallin 2) were less affected, indicating a high prevalence of latent tuberculosis (approximately 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 < or = .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-gamma 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.

• Authors: 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, Robert J Wilkinson
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 44 Issue 12 Pg. 1639-46 (Jun 15 2007) ISSN: 1537-6591 [Electronic] United States
• PMID: 17516410 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Bacterial
• Mycobacterium tuberculosis antigens
• Interferon-gamma

Topics

• AIDS-Related Opportunistic Infections (immunology, microbiology)
• Adult
• Antigens, Bacterial (blood, immunology)
• CD4 Lymphocyte Count
• Enzyme-Linked Immunosorbent Assay (methods)
• Female
• HIV Infections (epidemiology, immunology, microbiology)
• Humans
• Interferon-gamma (blood, metabolism)
• Male
• Middle Aged
• South Africa (epidemiology)
• T-Lymphocytes (metabolism)
• Tuberculin Test
• Tuberculosis (diagnosis, epidemiology, immunology)