Clinical, immunological, and epidemiological importance of antituberculosis T cell responses in HIV-infected Africans.
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.
Rangaka
Molebogeng X
MX
Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Diwakar
Lavanya
L
Seldon
Ronnett
R
van Cutsem
Gilles
G
Meintjes
Graeme A
GA
Morroni
Chelsea
C
Mouton
Priscilla
P
Shey
Muki S
MS
Maartens
Gary
G
Wilkinson
Katalin A
KA
Wilkinson
Robert J
RJ
D017088:AIDS-Related Opportunistic Infections / Q000276:immunology / Q000382:microbiology*; D000328:Adult; D000942:Antigens, Bacterial / Q000097:blood / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D015658:HIV Infections / Q000453:epidemiology / Q000276:immunology* / Q000382:microbiology*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D013019:South Africa / Q000453:epidemiology; D013601:T-Lymphocytes / Q000378:metabolism; D014374:Tuberculin Test; D014376:Tuberculosis / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology*
D000942:Antigens, Bacterial; C072681:Mycobacterium tuberculosis antigens; D007371:Interferon-gamma