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

Madeline Slater; Minh-Chi Tran; Lauren Platt; Lien T Luu; Ha T Phan; Phuong T Pham; Tam B Do; Hanh T Nguyen; Rajiv L Gaur; Julie Parsonnet; Adithya Cattamanchi; Robert Luo; Payam Nahid; Niaz Banaei

doi:10.1016/j.diagmicrobio.2015.05.007

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

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

Authors

Madeline Slater¹, Minh-Chi Tran², Lauren Platt³, Lien T Luu⁴, Ha T Phan⁴, Phuong T Pham⁴, Tam B Do⁴, Hanh T Nguyen⁴, Rajiv L Gaur⁵, Julie Parsonnet¹, Adithya Cattamanchi⁶, Robert Luo⁵, Payam Nahid⁶, Niaz Banaei⁷

Affiliations

¹ Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
² University of California, San Francisco School of Medicine, San Francisco, CA, USA.
³ Clinical Microbiology Laboratory, Stanford University Medical Center, Palo Alto, CA, USA.
⁴ Hanoi Lung Hospital, Hanoi, Vietnam.
⁵ Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
⁶ Division of Pulmonary and Critical Care Medicine, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA, USA.
⁷ Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA; Clinical Microbiology Laboratory, Stanford University Medical Center, Palo Alto, CA, USA.

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.

Publication types

Evaluation Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Female
Health Personnel
Humans
Immunologic Factors / metabolism*
Interferon-gamma Release Tests / methods*
Lipopolysaccharides / metabolism
Male
Middle Aged
Mycobacterium tuberculosis / immunology*
Poly I-C / metabolism
Prospective Studies
Sensitivity and Specificity
T-Lymphocytes / drug effects
T-Lymphocytes / immunology*
Tuberculosis / diagnosis*
United States
Vietnam

Substances

Immunologic Factors
Lipopolysaccharides
Poly I-C

Grants and funding

T32 AI052073/AI/NIAID NIH HHS/United States