Changes in the kinetics of intracellular IFN-γ production in TB patients during treatment

Gamma interferon (IFN-␥) release assays have been proven to be useful in the diagnosis of 5%). In conclusion, the IFN-␥ ELISPOT assay is a useful adjunct to current tests for diagnosis of active TB in China. The ELISPOT assay is more accurate than TST in identifying TB infections.Tuberculosis (TB) is a leading cause of morbidity and mortality throughout the world, with 95% of cases and 97% of all deaths occurring in high-prevalence countries, such as China, where the prevalence of active TB is as high as 367/100,000 population (10). For the effective and efficient control of TB in these countries, rapid diagnosis and treatment for active-TB patients are the mainstays of the TB control program. However, the current widely used tests, including acid-fast staining of sputum, mycobacterial culture, and antibody test, are not satisfactory for this purpose (4).Recently, commercial immunodiagnostic tests for TB infection have been introduced. These tests are based on the Mycobacterium tuberculosis-specific antigens early secretory antigenic target 6 (ESAT-6) and culture filtrate protein 10

Section: Discussionsupporting

confidence: 82%

Section: Resultsmentioning

confidence: 99%

Diagnosis of Active Tuberculosis in China Using an In-House Gamma Interferon Enzyme-Linked Immunospot Assay

Chen

Yang

Zhang

et al. 2009

“…Studies have shown that anti-TB treatment affected IGRA results with LTBI subjects (4,8,25) and active TB cases (16,23). In this study, the positive rate of the T-SPOT.TB assay in ATB patients with 3-to 6-month anti-TB treatment was significantly decreased compared with that for patients with 0 to 1 month of treatment (P Ͻ 0.005).…”

Section: Discussionmentioning

confidence: 54%

Evaluation of Gamma Interferon Release Assays Using Mycobacterium tuberculosis Antigens for Diagnosis of Latent and Active Tuberculosis in Mycobacterium bovis BCG-Vaccinated Populations

Zhang

Shao

et al. 2010

T-cell-based gamma interferon (IFN-␥) release assays (IGRAs) using Mycobacterium tuberculosis-specific antigens have shown higher sensitivity and specificity than the routine tuberculin skin test (TST). However, the effects of Mycobacterium bovis BCG vaccination and anti-tuberculosis (TB) treatment on dynamic T-cell responses to M. tuberculosis-specific antigens in active TB cases have rarely been investigated in regions where TB is endemic. Eighty-nine patients with active pulmonary TB (ATB) and 57 healthy controls (HC) from China were recruited and tested by sputum smear and culture, TSTs, and IGRAs with M. tuberculosis-specific antigens ESAT-6 and CFP-10 (T-SPOT.TB) as well as purified protein derivative (PPD) stimulation. All 146 participants were screened by the T-SPOT.TB assay at recruitment. T-SPOT.TB-positive rates in ATB and HC groups were 87.6% (78/89) and 21.1% (12/57), respectively. Of 38 ATB patients who were both TST and T-SPOT.TB tested, the positive rates were 73.7% (28/38) and 94.7% (36/38), respectively (P ‫؍‬ 0.0215), and those in the HC group were 62.3% (33/53) and 18.9% (10/53), respectively (P < 0.0001). The T-SPOT.TB-positive rates declined during TB treatment and were 94.4% (51/54), 86.4% (19/22), and 61.5% (8/13) for ATB patients receiving 0-to 1-month, 1-to 3-month, and 3-to 6-month anti-TB treatment, respectively. The IGRA is a most promising test for both active TB and latent TB infection (LTBI) diagnosis due to the improvement of its specificity and convenience, especially in the Mycobacterium bovis BCG-vaccinated population. Furthermore, the T-SPOT.TB assay using ESAT-6 and CFP-10 in ATB patients during anti-TB treatment could serve as a potential predictor of therapeutic efficacy.

“…IFN-␥ responses to antigen stimulation are easily induced in PBMC or whole blood and can be detected using simple technologies, such as enzymelinked immunosorbent assay (ELISA) or enzyme-linked immunosorbent spot assay (ELISPOT), since IFN-␥ is not labile and is usually produced in measurable quantities. Differences in the levels of IFN-␥ measured in culture supernatants of stimulated lymphocytes from TB patients and controls varied considerably depending on the study and were inconclusive as a diagnostic tool (40), probably due to nonstandardized sample handling and variable duration of stimulation with M. tuberculosis antigens (13).…”

mentioning

confidence: 99%

“…The tuberculin skin test (TST) utilizes PPD and has a number of drawbacks, notably that TST cross-reacts with the Mycobacterium bovis vaccine strain bacillus CalmetteGuérin (BCG) and other environmental mycobacteria, increasing the number of false positives (37). As IFN-␥ is required for a T helper 1 (Th1) response to M. tuberculosis, this cytokine has been measured ex vivo in serum (35, 39), sputum (35), bronchoalveolar lavage fluid (4), pleural effusions of TB patients (21, 25), or culture supernatants of peripheral blood mononuclear cells (PBMC) after in vitro stimulation with M. tuberculosis antigens (2,18,40). IFN-␥ responses to antigen stimulation are easily induced in PBMC or whole blood and can be detected using simple technologies, such as enzymelinked immunosorbent assay (ELISA) or enzyme-linked immunosorbent spot assay (ELISPOT), since IFN-␥ is not labile and is usually produced in measurable quantities.…”

mentioning

confidence: 99%

Effect of Chemotherapy on Whole-Blood Cytokine Responses to Mycobacterium tuberculosis Antigens in a Small Cohort of Patients with Pulmonary Tuberculosis

Bertholet

Horne

Laughlin

et al. 2011

The development of genomic and proteomic tools has enabled studies that begin to characterize the molecular targets of an effective host immune response to Mycobacterium tuberculosis, including understanding the specific immune responses associated with tuberculosis (TB) disease progression, disease resolution, and the development of latency. One application of such tools is the development of diagnostic reagents and assays useful as a test of cure. Such a test could be of considerable importance for the evaluation of new therapeutics. We and others have previously described immunodominant proteins of M. tuberculosis, including both vaccine and diagnostic candidates. In the present study, we describe the changes in immune responses to a panel of 71 M. tuberculosis antigens in six patients during the course of therapy. The levels of six cytokines were measured in 24-h whole-blood assays with these antigens, revealing that gamma interferon (IFN-␥), tumor necrosis factor (TNF), and interleukin-10 (IL-10) were differentially regulated in response to a subset of antigens. Therefore, measuring the production of these three cytokines in response to a panel of carefully selected M. tuberculosis proteins during the course of TB therapy might be a promising path toward the development of a test of cure and warrants further validation in larger cohorts of pulmonary TB patients. Tuberculosis (TB) caused by Mycobacterium tuberculosiscomplex bacilli is one of the leading causes of death worldwide (42). Upon exposure to M. tuberculosis, 30 to 40% of close contacts will develop TB infection, of whom 5% would be expected to develop active disease within a 24-month period while the other 95% enter a state of controlled latent TB infection (LTBI), which can reactivate later in life following decreased immunocompetence of the host. T cells, both CD4 ϩ and CD8 ϩ , and the cytokines gamma interferon (IFN-␥) and tumor necrosis factor (TNF) play important roles in the prevention of active disease and the control of LTBI, as demonstrated by gene-knockout animal models and human subjects with mutations affecting the expression of these two cytokines (17).The traditional diagnosis of active TB disease relies on positive identification of acid-fast bacilli (AFB) in a sputum smear or M. tuberculosis identified in culture and is supported by delayed-type hypersensitivity reactions to intradermal injection of M. tuberculosis-specific and nonspecific purified protein derivative (PPD). The tuberculin skin test (TST) utilizes PPD and has a number of drawbacks, notably that TST cross-reacts with the Mycobacterium bovis vaccine strain bacillus CalmetteGuérin (BCG) and other environmental mycobacteria, increasing the number of false positives (37). As IFN-␥ is required for a T helper 1 (Th1) response to M. tuberculosis, this cytokine has been measured ex vivo in serum (35, 39), sputum (35), bronchoalveolar lavage fluid (4), pleural effusions of TB patients (21, 25), or culture supernatants of peripheral blood mononuclear cells (PBMC) after in vitro...