title: In vitro immunomodulation for enhancing T cell-based diagnosis of Mycobacterium tuberculosis infection.
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.
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Madeline
authors.initials: M
authors.lastname: Slater
authors.affiliation: University of California, San Francisco School of Medicine, San Francisco, CA, USA.
authors.forename: Minh-Chi
authors.initials: MC
authors.lastname: Tran
authors.affiliation: Clinical Microbiology Laboratory, Stanford University Medical Center, Palo Alto, CA, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Platt
authors.affiliation: Hanoi Lung Hospital, Hanoi, Vietnam.
authors.forename: Lien T
authors.initials: LT
authors.lastname: Luu
authors.affiliation: Hanoi Lung Hospital, Hanoi, Vietnam.
authors.forename: Ha T
authors.initials: HT
authors.lastname: Phan
authors.affiliation: Hanoi Lung Hospital, Hanoi, Vietnam.
authors.forename: Phuong T
authors.initials: PT
authors.lastname: Pham
authors.affiliation: Hanoi Lung Hospital, Hanoi, Vietnam.
authors.forename: Tam B
authors.initials: TB
authors.lastname: Do
authors.affiliation: Hanoi Lung Hospital, Hanoi, Vietnam.
authors.forename: Hanh T
authors.initials: HT
authors.lastname: Nguyen
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Rajiv L
authors.initials: RL
authors.lastname: Gaur
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Parsonnet
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA, USA.
authors.forename: Adithya
authors.initials: A
authors.lastname: Cattamanchi
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Luo
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA, USA.
authors.forename: Payam
authors.initials: P
authors.lastname: Nahid
authors.affiliation: 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.
authors.forename: Niaz
authors.initials: N
authors.lastname: Banaei
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006282:Health Personnel; D006801:Humans; D007155:Immunologic Factors / Q000378:metabolism*; D059425:Interferon-gamma Release Tests / Q000379:methods*; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011070:Poly I-C / Q000378:metabolism; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014376:Tuberculosis / Q000175:diagnosis*; D014481:United States; D014744:Vietnam
chemical_list: D007155:Immunologic Factors; D008070:Lipopolysaccharides; D011070:Poly I-C
keywords: Interferon gamma release assays; Pathogen associated molecular patterns; Quantiferon; Tuberculosis