Tuberculosis antigen‐specific immune responses can be detected using enzyme‐linked immunospot technology in human immunodeficiency virus (HIV)‐1 patients with advanced disease

Department of Immunology, Imperial College, Chelsea & Westminster Hospital, London, UK.
Clinical & Experimental Immunology (Impact Factor: 3.04). 11/2007; 150(2):238-44. DOI: 10.1111/j.1365-2249.2007.03477.x
Source: PubMed


There are limited data on the efficacy of T cell-based assays to detect tuberculosis (TB) antigen-specific responses in immune-deficient human immunodeficiency virus (HIV) patients. The aim of this study is to determine whether TB antigen-specific immune responses can be detected in patients with HIV-1 infection, especially in those with advanced disease (CD4 T cell count < 300 cells/microl). An enzyme-linked immunospot (ELISPOT) assay, which detects interferon (IFN)-gamma secreted by T cells exposed to TB antigens, was used to assess specific immune responses in a prospective study of 201 HIV-1-infected patients with risk factors for TB infection, attending a single HIV unit. The performance of the ELISPOT assay to detect TB antigen-specific immune responses is independent of CD4 T cell counts in HIV-1 patients. The sensitivity and specificity of this assay for the diagnosis of active tuberculosis does not differ significantly from values obtained in immunocompetent subjects. The negative predictive value of the TB ELISPOT test is 98.2%. A positive predictive value of 86% for the diagnosis of active tuberculosis was found when the combined number of early secretory antigen target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) IFN-gamma spots to CD4 T cell count ratio was > 1.5. TB antigen-specific immune responses can be detected in HIV patients with low CD4 T cell counts using ELISPOT technology in a routine diagnostic laboratory and is a useful test to exclude TB infection in immune-deficient HIV-1 patients. A combination of TB antigen-specific IFN-gamma responses and CD4 T cell counts has the potential to distinguish active tuberculosis from latent infection.

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Available from: Alan Steel, Jan 22, 2014
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    • "This prohibited us from evaluating the predictive value of IGRAs for the development of active tuberculosis among HIV-infected patients. Further studies are needed to assess the predictive value of IGRAs for active TB, especially among immunocompromised patients such as those with HIV infection [31-33]. "
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    ABSTRACT: Improved tests to diagnose latent TB infection (LTBI) are needed. We sought to evaluate the performance of two commercially available interferon-gamma release assays (IGRAs) compared to the tuberculin skin test (TST) for the diagnosis of LTBI and to identify risk factors for LTBI among HIV-infected individuals in Georgia, a country with high rates of TB. HIV-patients were enrolled from the National AIDS Center in Tbilisi, Georgia. After providing informed consent, each participant completed a questionnaire, had blood drawn for QuantiFERON-TB Gold in-Tube (QFT-GIT) and T-SPOT.TB testing and had a TST placed. The TST was read at 48--72 hrs with >= 5 mm induration considered positive. Between 2009--2011, 240 HIV-infected persons (66% male) with a median age of 38 years and a median CD4 count of 255 cells/mul (IQR: 124--412) had diagnostic testing for LTBI performed. 94% had visible evidence of a BCG scar. The TST was positive in 41 (17%) patients; QFT-GIT in 70 (29%); and T-SPOT.TB in 56 (24%). At least one diagnostic test was positive in 109 (45%) patients and only among 13 (5%) patients were all three tests positive. Three (1%) QFT-GIT and 19 (8%) T-SPOT.TB test results were indeterminate. The agreement among all pairs of tests was poor: QFT-GIT vs. T-SPOT.TB (kappa = 0.18, 95% CI .07-.30), QFT-GIT vs. TST (kappa = 0.29, 95% CI .16-.42), and TST vs. T-SPOT.TB (kappa = 0.22, 95% CI .07-.29). Risk factors for LTBI varied by diagnostic test and none showed associations between positive test results and well-known risk factors for TB, such as imprisonment, drug abuse and immunological status. A high proportion of HIV patients had at least one positive diagnostic test for LTBI; however, there was very poor agreement among all tests. This lack of agreement makes it difficult to know which test is superior and most appropriate for LTBI testing among HIV-infected patients. While further follow-up studies will help determine the predictive ability of different LTBI tests, improved modalities are needed for accurate detection of LTBI and assessment of risk of developing active TB among HIV-infected patients.
    BMC Infectious Diseases 11/2013; 13(1):513. DOI:10.1186/1471-2334-13-513 · 2.61 Impact Factor
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    • "The accuracy of IGRA tests have been tested in distinct subpopulations such as children [38, 47, 48, 56, 78–84], PLWHA [23, 29, 39, 40, 47, 54, 55, 85–103], other immunosuppressed patients (those with renal disease or in use of tumor necrosis factor-alpha inhibitors), [104–106] and healthcare workers [53]. "
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    ABSTRACT: A profusion of articles have been published on the accuracy and uses of interferon-gamma releasing assays. Here we review the clinical applications, advantages, and limitations of the tuberculin skin test and interferon-gamma release assays and provide an overview of the most recent systematic reviews conducted for different indications for the use of these tests. We conclude that both tests are accurate to detect latent tuberculosis, although interferon-gamma release assays have higher specificity than tuberculin skin testing in BCG-vaccinated populations, particularly if BCG is received after infancy. However, both tests perform poorly to predict risk for progression to active tuberculosis. Interferon-gamma release assays have significant limitations in serial testing because of spontaneous variability and lack of a validated definition of conversion and reversion, making it difficult for clinicians to interpret changes in category (conversions and reversions). So far, the most important clinical evidence, that is, that isoniazid preventive therapy reduces the risk for progression to disease, has been produced only in tuberculin skin test-positive individuals.
    Pulmonary Medicine 02/2013; 2013(4):601737. DOI:10.1155/2013/601737
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    • "Differentiating which HIV+ patients are at risk of developing active tuberculosis and who will benefit from preventative treatment from those who are not at risk and do not require preventative treatment is a pressing clinical need. To date, 4 longitudinal studies have assessed the ability of IGRAs to predict which HIV+ patients will develop active TB: 3 with QFT-IT [33], [34], [35] and one with T-SPOT.TB [36]. All reported that patients with positive IGRA results had a similarly higher risk of developing active tuberculosis, although all studies had limitations [28]. "
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    ABSTRACT: Interferon gamma release assays (IGRAs) are used to diagnose latent tuberculosis infection. Two IGRAs are commercially available: the Quantiferon TB Gold In Tube (QFT-IT) and the T-SPOT.TB. There is debate as to which test to use in HIV+ individuals. Previous publications from high TB burden countries have raised concerns that the sensitivity of the QFT-IT assay, but not the T-SPOT.TB, may be impaired in HIV+ individuals with low CD4+ T-cell counts. We sought to compare the tests in a low TB burden setting. T-SPOT.TB, QFT-IT, and tuberculin skin tests (TST) were performed in HIV infected individuals. Results were related to patient characteristics. McNemar's test, multivariate regression and correlation analysis were carried out using SPSS (SPSS Inc). 256 HIV infected patients were enrolled in the study. The median CD4+ T-cell count was 338 cells/µL (range 1-1328). 37 (14%) patients had a CD4+ T-cell count of <100 cells/µL. 46/256 (18% ) of QFT-IT results and 28/256 (11%) of T-SPOT.TB results were positive. 6 (2%) of QFT-IT and 18 (7%) of T-SPOT.TB results were indeterminate. An additional 9 (4%) of T-SPOT.TB results were unavailable as tests were not performed due to insufficient cells or clotting of the sample. We found a statistically significant association between lower CD4+ T-cell count and negative QFT-IT results (OR 1.055, p = 0.03), and indeterminate/unavailable T-SPOT.TB results (OR 1.079, p = 0.02). In low TB prevalence settings, the QFT-IT yields more positive and fewer indeterminate results than T-SPOT.TB. Negative results on the QFT-IT and indeterminate/unavailable results on the T-SPOT.TB were more common in individuals with low CD4+ T-cell counts.
    PLoS ONE 01/2013; 8(1):e53330. DOI:10.1371/journal.pone.0053330 · 3.23 Impact Factor
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