title: Discriminating Active Tuberculosis from Latent Tuberculosis Infection by flow cytometric measurement of CD161-expressing T cells.
abstract: Interferon-gamma Release Assays (IGRAs) significantly increases the possibility for early diagnosis of tuberculosis, but IGRAs alone cannot discriminate active TB from LTBI. Therefore, fast and reliable discrimination of active tuberculosis, especially bacteriology negative tuberculosis, from LTBI is a great necessity. Here we established an assay based on flow cytometric multiparameter assay assessing expression of CD161 along with CD3, CD4, and CD8, whereby a set of indices formulated by the percentages of CD3(+)CD161(+), CD3(+)CD4(+)CD161(+) and CD3(+)CD8(+)CD161(+) T cells multiplied with lymphocyte/monocyte ratio were established. Application of the CD3(+)CD8(+)CD161(+) index to compare a cohort of active tuberculosis with a cohort of LTBI or health control yielded 0.7662 (95% confidence interval [CI] 0.6559-0.8552) or 0.7922 (95% CI 0.6846-0.8763) for sensitivity and 0.9048 (95% CI 0.8209-0.9580) or 0.8939 (95% CI 0.8392-0.9349) for specificity when the TB cohort was AFB(+); the corresponding results were 0.7481 (95% CI 0.6648-0.8198) or 0.7557 (95% CI 0.6730-0.8265) for sensitivity and 0.8571 (95% CI 0.7637-0.9239) or 0.8603 (95% CI 0.8008-0.9075) for specificity when the TB cohort was AFB(-). Our results reveal that in combination with IGRAs, CD161-based indices provide a novel, fast diagnostic solution addressing the limitation of current tuberculosis diagnostics.
authors.affiliation: Guangdong (Shenzhen) Key Laboratory for Diagnosis &Treatment of Emerging Infectious Diseases.|Shenzhen Key Laboratory of Infection &Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, China.
authors.forename: Qianting
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Guangdong (Shenzhen) Key Laboratory for Diagnosis &Treatment of Emerging Infectious Diseases.|Shenzhen Key Laboratory of Infection &Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, China.|Institute of Microbiology, Chinese Academy of Sciences, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Shenzhen Key Laboratory of Infection &Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Guangdong (Shenzhen) Key Laboratory for Diagnosis &Treatment of Emerging Infectious Diseases.|Shenzhen Key Laboratory of Infection &Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: Guangdong (Shenzhen) Key Laboratory for Diagnosis &Treatment of Emerging Infectious Diseases.|Shenzhen Key Laboratory of Infection &Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, China.
authors.forename: Mingxia
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Guangdong (Shenzhen) Key Laboratory for Diagnosis &Treatment of Emerging Infectious Diseases.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Institute of Pathogen Biology, Chinese Academy of Medical Sciences, China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Respiratory Diseases, Shenzhen Futian Hospital, China.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Guangdong (Shenzhen) Key Laboratory for Diagnosis &Treatment of Emerging Infectious Diseases.
authors.forename: Guofang
authors.initials: G
authors.lastname: Deng
authors.affiliation: Shenzhen Key Laboratory of Infection &Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, China.
authors.forename: Qunyi
authors.initials: Q
authors.lastname: Deng
authors.affiliation: Guangdong (Shenzhen) Key Laboratory for Diagnosis &Treatment of Emerging Infectious Diseases.
authors.forename: Boping
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, USA.
authors.forename: Hardy
authors.initials: H
authors.lastname: Kornfeld
authors.affiliation: Guangdong (Shenzhen) Key Laboratory for Diagnosis &Treatment of Emerging Infectious Diseases.|Shenzhen Key Laboratory of Infection &Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, China.
authors.forename: Xinchun
authors.initials: X
authors.lastname: Chen
mesh_terms: D000954:Antigens, Surface / Q000378:metabolism; D015415:Biomarkers; D015331:Cohort Studies; D003937:Diagnosis, Differential; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D016130:Immunophenotyping; D059425:Interferon-gamma Release Tests; D055985:Latent Tuberculosis / Q000097:blood / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D018655:Lymphocyte Count; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism*; D015203:Reproducibility of Results; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D014376:Tuberculosis / Q000097:blood / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology
chemical_list: D000954:Antigens, Surface; D015415:Biomarkers; D055651:NK Cell Lectin-Like Receptor Subfamily B