title: A TB antigen-stimulated CXCR3 ligand assay for the diagnosis of active pulmonary TB.
abstract: BACKGROUND
  The ligands for CXC chemokine receptor 3 (CXCR3) recruit T-helper type 1 cells, which play a major role in cell-mediated immunity in TB.
  
  
  METHODS
  A total of 409 subjects were enrolled. The study population comprised 186 patients with active TB, 58 patients with non-TB pulmonary diseases, 50 control subjects with a positive interferon (IFN)-γ release assay (IGRA) result, and 115 control subjects with a negative IGRA result. Whole-blood samples were collected using IGRA methodology. After incubation, plasma IFN-γ levels and two CXCR3 ligands, IFN-inducible T-cell α-chemoattractant (I-TAC, CXCL11) and monokine induced by IFN-γ (MIG, CXCL9), were measured by enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) analysis was performed. Sensitivity and specificity were based on cutoff values selected to maximize the Youden index.
  
  
  RESULTS
  The TB antigen-stimulated levels of IFN-γ, I-TAC, and MIG were significantly increased in the active pulmonary TB group compared with all other groups. From ROC analysis, for the diagnosis of active TB, I-TAC and MIG outperformed IFN-γ in all comparisons with the IGRA-positive and -negative control groups and the non-TB pulmonary disease group. The areas under the curve (95% CI) for differentiating active pulmonary TB from all other groups were 0.893 (0.864-0.924) for IFN-γ, 0.962 (0.946-0.978) for I-TAC, and 0.944 (0.922-0.965) for MIG. Sensitivity and specificity were 90.3% and 90.7%, respectively, for I-TAC; 92.5% and 85.2% for MIG; and 84.9% and 79.8% for IFN-γ.
  
  
  CONCLUSIONS
  TB antigen-stimulated assays of I-TAC and MIG may be useful surrogate markers in the diagnosis of active pulmonary TB.
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon, South Korea.
authors.forename: Wou Young
authors.initials: WY
authors.lastname: Chung
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon, South Korea.
authors.forename: Keu Sung
authors.initials: KS
authors.lastname: Lee
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon, South Korea.
authors.forename: Yun Jung
authors.initials: YJ
authors.lastname: Jung
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon, South Korea.
authors.forename: Hye Lim
authors.initials: HL
authors.lastname: Lee
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon, South Korea.
authors.forename: Young Sun
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon, South Korea.
authors.forename: Joo Hun
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon, South Korea.
authors.forename: Seung Soo
authors.initials: SS
authors.lastname: Sheen
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon, South Korea. Electronic address: parkkj@ajou.ac.kr.
authors.forename: Kwang Joo
authors.initials: KJ
authors.lastname: Park
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007111:Immunity, Cellular; D008024:Ligands; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000302:isolation & purification; D012372:ROC Curve; D054367:Receptors, CXCR3 / Q000378:metabolism*; D012189:Retrospective Studies; D013183:Sputum / Q000382:microbiology; D018417:Th1 Cells / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; C515187:CXCR3 protein, human; D008024:Ligands; D054367:Receptors, CXCR3