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. 2015 Sep;83(1):41-5.
doi: 10.1016/j.diagmicrobio.2015.05.007. Epub 2015 May 19.

In vitro immunomodulation for enhancing T cell-based diagnosis of Mycobacterium tuberculosis infection

Affiliations

In vitro immunomodulation for enhancing T cell-based diagnosis of Mycobacterium tuberculosis infection

Madeline Slater et al. Diagn Microbiol Infect Dis. 2015 Sep.

Abstract

Interferon-gamma release assays have limited sensitivity for detecting latent tuberculosis infection. In this study, we determine if the addition of immunomodulators to the QuantiFERON-TB Gold In-Tube (QFT-GIT) increased test sensitivity without compromising specificity. We prospectively compared QFT-GIT results with and without incubation with 2 immunomodulators (lipopolysaccharide [LPS] and polyinosine-polycytidylic acid [PolyIC]) in 2 cohorts-113 culture-confirmed tuberculosis (TB) subjects in Hanoi, Vietnam, and 226 documented QFT-GIT-negative, low TB risk health care workers undergoing annual TB screening at a US academic institution. Sensitivity of the tests in TB subjects was 84.1% with the standard QFT-GIT and 85.8% and 74.3% after incubation with LPS and PolyIC, respectively. Specificity in low TB risk health care workers was 100% with the standard QFT-GIT by design and 86.7% with LPS and 63.3% with PolyIC. In conclusion, use of the 2 immunomodulators did not improve sensitivity of the QFT-GIT in TB patients and reduced specificity in low-risk health care workers.

Keywords: Interferon gamma release assays; Pathogen associated molecular patterns; Quantiferon; Tuberculosis.

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Figures

Fig. 1
Fig. 1
Flow chart of subject inclusion.
Fig. 2
Fig. 2
Quantitative results of the standard QFT and QFT with LPS or PolyIC in the cohort with treated TB. Boxes show interquartile ranges, and the lower whisker represents data within 1.5 times the IQR of the lower quartile, and the upper whisker represents data within 1.5 times the IQR of the upper quartile. Dots represent outliers above 1.5 times the IQR of the upper quartile. The reference line at TB response of 0.35 IU/mL is the QFT cutoff. QFT = QuantiFERON-TB Gold In Tube; TB response = TB antigen minus nil; IQR = interquartile range.
Fig. 3
Fig. 3
Quantitative results of the standard QFT and QFT with LPS or PolyIC in the uninfected cohort. Boxes show interquartile ranges, and the lower whisker represents data within 1.5 times the IQR of the lower quartile, and the upper whisker represents data within 1.5 times the IQR of the upper quartile. Dots represent outliers above 1.5 times the IQR of the upper quartile. The reference line at TB response of 0.35 IU/mL is the QFT cutoff. QFT = QuantiFERON-TB Gold In Tube; TB response = TB antigen minus nil.

References

    1. Abu-Raddad LJ, Sabatelli L, Achterberg JT, Sugimoto JD, Longini IM, Jr, Dye C, et al. Epidemiological benefits of more-effective tuberculosis vaccines, drugs, and diagnostics. Proc Natl Acad Sci U S A. 2009;106:13980–5. - PMC - PubMed
    1. Blower SM, McLean AR, Porco TC, Small PM, Hopewell PC, Sanchez MA, et al. The intrinsic transmission dynamics of tuberculosis epidemics. Nat Med. 1995;1:815–21. - PubMed
    1. Cattamanchi A, Smith R, Steingart KR, Metcalfe JZ, Date A, Coleman C, et al. Interferon-gamma release assays for the diagnosis of latent tuberculosis infection in HIV-infected individuals: a systematic review and meta-analysis. J Acquir Immune Defic Syndr. 2011;56:230–8. - PMC - PubMed
    1. Diel R, Goletti D, Ferrara G, Bothamley G, Cirillo D, Kampmann B, et al. Interferon-gamma release assays for the diagnosis of latent Mycobacterium tuberculosis infection: a systematic review and meta-analysis. Eur Respir J. 2011;37:88–99. - PubMed
    1. Farhat M, Greenaway C, Pai M, Menzies D. False-positive tuberculin skin tests: what is the absolute effect of BCG and non-tuberculous mycobacteria? Int J Tuberc Lung Dis. 2006;10:1192–204. - PubMed

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