scholarly journals Evaluation of Gamma Interferon Immune Response Elicited by the Newly Constructed PstS-1(285-374):CFP10 Fusion Protein To Detect Mycobacterium tuberculosis Infection

2014 ◽  
Vol 21 (4) ◽  
pp. 552-560 ◽  
Author(s):  
Leonardo Silva de Araujo ◽  
Fernanda Carvalho de Queiroz Mello ◽  
Nidai de Bárbara Moreira da Silva ◽  
Janaina Aparecida Medeiros Leung ◽  
Silvia Maria Almeida Machado ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Tuberculin Skin Test ◽  
Skin Test ◽  
Positive Tuberculin Skin Test ◽  
Gamma Interferon ◽  
Preventative Treatment ◽  
Mycobacterium Tuberculosis Infection ◽  
Content Type ◽  
Ifn Γ ◽  
First Time

ABSTRACTThe PstS1 antigen is highly immunogenic, principally when combined with CFP10 during both latent and active TB infection. In the present study, a selectedpstS1gene fragment was cloned, fused with CFP10, and expressed inEscherichia coli. The product [PstS-1(285-374):CFP10] was compared to the recombinant fused RD1 (region of deletion 1) protein (ESAT-6:CFP10) in detectingMycobacterium tuberculosisinfection in 108 recent contacts of pulmonary tuberculosis (TB) cases, considering a positive tuberculin skin test (TST) to be the baseline. The release of gamma interferon (IFN-γ) in 22-h whole-blood and 5-day lymphocyte stimulation assays primed with each antigen was determined. All contacts were clinically followed for up to 1 year, and 87% of the tuberculin skin test-positive (TSTpositive) patients accepted preventative treatment. Concerning the IFN-γ response to PstS-1(285-374):CFP10 in the 22-h and 5-day assays, a slight increase in contact-TSTpositivedetection was observed (23/54 and 26/54) compared to the level seen with the RD1 protein (18/54 and 24/54) whereas in the TSTnegativegroup, similarly lower numbers (≤5/48) of responders were achieved for both antigens, except for RD1 in the 5-day assay (8/48). By combining the IFN-γ responders to both antigens in the 5-day assays, slightly higher increases in positivity were found in the TSTpositive(32/54) and TSTnegative(10/48) groups. Two of 12 untreated TSTpositivecontacts progressed to active TB and were concordantly positive in all assays, except for one contact who lacked positivity in the RD1 5-day assay. We demonstrated for the first time that PstS-1(285-374):CFP10 slightly increased contact positivity and detection of active disease progression, suggesting its potential application as a TB infection marker.

scholarly journals Comparison of Two Commercially Available Gamma Interferon Blood Tests for Immunodiagnosis of Tuberculosis

2007 ◽  
Vol 15 (1) ◽  
pp. 168-171 ◽  
Author(s):  
Jose Domínguez ◽  
Juan Ruiz-Manzano ◽  
Malú De Souza-Galvão ◽  
Irene Latorre ◽  
Celia Milà ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Tuberculin Skin Test ◽  
Skin Test ◽  
Mycobacterium Bovis ◽  
Latent Infection ◽  
Positive Tuberculin Skin Test ◽  
Gamma Interferon ◽  
Bcg Vaccination ◽  
Blood Tests

ABSTRACT We evaluated the T-SPOT.TB and Quantiferon-TB Gold In tube (QFN-G-IT) tests for diagnosing Mycobacterium tuberculosis infection. T-SPOT.TB was more sensitive than QFN-G-IT in diagnosing both active and latent infection. Both gamma interferon tests were unaffected by prior Mycobacterium bovis BCG vaccination. Among children who were not BCG vaccinated but had a positive tuberculin skin test, QFN-G-IT was negative in 53.3% of cases, and T-SPOT.TB was negative in 50% of cases.

scholarly journals Long-Incubation-Time Gamma Interferon Release Assays in Response to Purified Protein Derivative, ESAT-6, and/or CFP-10 for the Diagnosis of Mycobacterium tuberculosis Infection in Children

2013 ◽  
Vol 21 (2) ◽  
pp. 111-118 ◽  
Author(s):  
K. Schepers ◽  
F. Mouchet ◽  
V. Dirix ◽  
I. De Schutter ◽  
K. Jotzo ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Incubation Time ◽  
Gamma Interferon ◽  
Skin Tests ◽  
Mycobacterium Tuberculosis Infection ◽  
Content Type ◽  
X Ray ◽  
Purified Protein Derivative ◽  
Chest X Ray ◽  
Ifn Γ

ABSTRACTThe diagnosis of childhood active tuberculosis (aTB) and latentMycobacterium tuberculosis(M. tuberculosis) infection (LTBI) remains a challenge, and the replacement of tuberculin skin tests (TST) with commercialized gamma interferon (IFN-γ) release assays (IGRA) is not currently recommended. Two hundred sixty-six children between 1 month and 15 years of age, 214 of whom were at risk of recentM. tuberculosisinfection and 51 who were included as controls, were prospectively enrolled in our study. According to the results of a clinical evaluation, TST, chest X ray, and microbiological assessment, each children was classified as noninfected, having LTBI, or having aTB. Long-incubation-time purified protein derivative (PPD), ESAT-6, and CFP-10 IGRA were performed and evaluated for their accuracy in correctly classifying the children. Whereas both TST and PPD IGRA were suboptimal for detecting aTB, combining the CFP-10 IGRA with a TST or with a PPD IGRA allowed us to detect all the children with aTB with a specificity of 96% for children who were positive for the CFP-10 IGRA. Moreover, the combination of the CFP-10 IGRA and PPD IGRA detected 96% of children who were eventually classified as having LTBI, but a strong IFN-γ response to CFP-10 (defined as >500 pg/ml) was highly suggestive of aTB, at least among the children who were <3 years old. The use of long-incubation-time CFP-10 IGRA and PPD IGRA should help clinicians to quickly identify aTB or LTBI in young children.

scholarly journals Spontaneous Phthiocerol Dimycocerosate-Deficient Variants of Mycobacterium tuberculosis Are Susceptible to Gamma Interferon-Mediated Immunity

2011 ◽  
Vol 79 (7) ◽  
pp. 2829-2838 ◽  
Author(s):  
Meghan A. Kirksey ◽  
Anna D. Tischler ◽  
Roxane Siméone ◽  
Katherine B. Hisert ◽  
Swapna Uplekar ◽  
...  
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Point Mutation ◽  
Chronic Phase ◽  
Gamma Interferon ◽  
Wild Type ◽  
Content Type ◽  
Virulence Attenuation ◽  
Ifn Γ ◽  
Phthiocerol Dimycocerosate

ABSTRACTOnset of the adaptive immune response in mice infected withMycobacterium tuberculosisis accompanied by slowing of bacterial replication and establishment of a chronic infection. Stabilization of bacterial numbers during the chronic phase of infection is dependent on the activity of the gamma interferon (IFN-γ)-inducible nitric oxide synthase (NOS2). Previously, we described a differential signature-tagged mutagenesis screen designed to identifyM. tuberculosis“counterimmune” mechanisms and reported the isolation of three mutants in the H37Rv strain background containing transposon insertions in therv0072,rv0405, andrv2958cgenes. These mutants were impaired for replication and virulence in NOS2−/−mice but were growth-proficient and virulent in IFN-γ−/−mice, suggesting that the disrupted genes were required for bacterial resistance to an IFN-γ-dependent immune mechanism other than NOS2. Here, we report that the attenuation of these strains is attributable to an underlying transposon-independent deficiency in biosynthesis of phthiocerol dimycocerosate (PDIM), a cell wall lipid that is required for full virulence in mice. We performed whole-genome resequencing of a PDIM-deficient clone and identified a spontaneous point mutation in the putative polyketide synthase PpsD that results in a G44C amino acid substitution. We demonstrate by complementation with the wild-typeppsDgene and reversion of theppsDgene to the wild-type sequence that theppsD(G44C) point mutation is responsible for PDIM deficiency, virulence attenuation in NOS2−/−and wild-type C57BL/6 mice, and a growth advantagein vitroin liquid culture. We conclude that PDIM biosynthesis is required forM. tuberculosisresistance to an IFN-γ-mediated immune response that is independent of NOS2.

scholarly journals Kinetics of a Tuberculosis-Specific Gamma Interferon Release Assay in Military Personnel with a Positive Tuberculin Skin Test

2010 ◽  
Vol 17 (6) ◽  
pp. 937-943 ◽  
Author(s):  
Sigrid E. van Brummelen ◽  
Anja M. Bauwens ◽  
Noël J. Schlösser ◽  
Sandra M. Arend
Keyword(s):  
Tuberculin Skin Test ◽  
Skin Test ◽  
Military Personnel ◽  
False Positive ◽  
Quantitative Result ◽  
Positive Tuberculin Skin Test ◽  
Gamma Interferon ◽  
Health Care Work ◽  
Release Assay ◽  
Kinetics Of

ABSTRACT Treatment of latent Mycobacterium tuberculosis infection on the basis of the tuberculin skin test (TST) result is inaccurate due to the false-positive TST results that occur after Mycobacterium bovis BCG vaccination or exposure to nontuberculous mycobacteria (NTM). Gamma interferon release assays (IGRAs) are based on M. tuberculosis-specific antigens. In a previous study among BCG-naïve military employees, a positive TST result after deployment was mostly associated with a negative IGRA result, suggesting exposure to NTM. Data regarding the kinetics of IGRAs are limited and controversial. The present study aimed to reassess the rate of false-positive TST results and to evaluate the kinetics of the Quantiferon TB Gold In-Tube assay (QFT-Git) in military personnel with a positive TST result. QFT-Git was performed at the time of inclusion in the study and was repeated after 2, 6, 12, and 18 or 24 months. Of 192 participants, 17 were recruits and 175 were screened after deployment (n = 169) or because of travel or health care work. Baseline positive QFT-Git results were observed in 7/17 (41.2%) and 12/174 (6.9%) participants, respectively. During follow-up, a negative QFT-Git result remained negative in 163/165 (98.8%) participants. Of 18 subjects with an initial positive QFT-Git result, reversion to a negative result occurred in 1/6 (16%) recruits, whereas it occurred in 8/12 (66%) subjects after deployment or with other risk factors (P = 0.046). The quantitative result was significantly lower in subjects with reversion than in those with consistent positive results (P = 0.017). This study confirmed a low rate of positive QFT-Git results among military personnel with a positive TST result after deployment, supporting the hypothesis of exposure to NTM. Reversion of the majority of initially low-positive QFT-Git results indicates that QFT-Git may be useful for the diagnosis of later reinfections.

scholarly journals Comparison of a New ESAT-6/CFP-10 Peptide-Based Gamma Interferon Assay and a Tuberculin Skin Test for Tuberculosis Screening in a Moderate-Risk Population

2006 ◽  
Vol 13 (1) ◽  
pp. 53-58 ◽  
Author(s):  
Emaeil Porsa ◽  
Lee Cheng ◽  
Michael M. Seale ◽  
George L. Delclos ◽  
Xin Ma ◽  
...  
Keyword(s):  
African American ◽  
Tuberculin Skin Test ◽  
Skin Test ◽  
The United States ◽  
Gamma Interferon ◽  
Test Results ◽  
Bcg Vaccination ◽  
Ifn Γ ◽  
Foreign Birth ◽  
American Ethnicity

ABSTRACT Screening for latent tuberculosis infection (LTBI) with Mantoux tuberculin skin test (TST) has many limitations, including false-positive results due to exposure to Mycobacterium other than tuberculosis (TB) and BCG vaccination. A total of 474 adult inmates in a county jail were screened for LTBI using TST and a new ESAT-6/CFP-10 peptide-based whole-blood gamma interferon (IFN-γ) assay. LTBI prevalence was 9.0 and 5.4% as determined by TST and IFN-γ assay, respectively. Overall, agreement between test results was 90% (κ = 0.25). Positive TST results were significantly associated with increased age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01 to 1.08), African-American ethnicity (OR, 4.97; 95% CI, 1.58 to 15.68), foreign birth (OR, 20.20; 95% CI, 4.21 to 97.02) and prior incarceration (OR, 6.19; 95% CI, 1.48 to 25.95). Positive IFN-γ assay results were significantly associated with African-American ethnicity (OR, 5.58; 95% CI, 1.16 to 26.74). Factors associated with statistically significant discordance between TST and IFN-γ assay results were African-American ethnicity (OR, 0.29; 95% CI, 0.11 to 0.77), foreign birth (OR, 0.23; 95% CI, 0.07-0.80), and prior incarceration (OR, 0.06; 95% CI, 0.01-0.50). Among subjects born in the United States, African-American ethnicity was the only variable significantly associated with positive test results for both TST (OR, 4.26; 95% CI, 1.38 to 13.16) and IFN-γ assay (OR, 5.74; 95% CI, 1.19 to 27.75) and remained associated with statistically significant discordance between TST and IFN-γ assay results. The reactivity of the new IFN-γ assay is unaffected by prior BCG vaccination or serial TSTs but may be diminished in African-Americans. Future longitudinal studies are needed to assess the sensitivity and specificity of this new assay in detecting LTBI.

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