title: Adjunctive biomarkers for improving diagnosis of tuberculosis and monitoring therapeutic effects.
abstract: OBJECTIVE
  To identify host biomarkers associated with latent tuberculosis infection (LTBI), active tuberculosis (TB), and nontuberculous mycobacteria (NTM) diseases to improve diagnosis and effective anti-TB treatment.
  
  
  METHODS
  Active TB and NTM patients at diagnosis, recent TB contacts, and normal healthy subjects were recruited. Tuberculin skin tests, QuantiFERON-TB Gold In-Tube tests, and multiplex bead arrays with 17 analytes were performed. TB patients were re-evaluated after 2 and 6 months of treatment.
  
  
  RESULTS
  Mycobacterium tuberculosis (M. tb) antigen-specific IFN-γ, IL-2, and CXCL10 responses were significantly higher in active TB and LTBI compared with controls (P < 0.01). Only serum VEGF levels varied between the active TB and LTBI groups (AUC = 0.7576, P < 0.001). Active TB and NTM diseases were differentiated by serum IL-2, IL-9, IL-13, IL-17, TNF-α and sCD40L levels (P < 0.05). Increased sCD40L and decreased M. tb antigen-specific IFN-γ levels correlated with sputum clearance of M. tb after 2 months of treatment (P < 0.001).
  
  
  CONCLUSIONS
  Serum IL-2, IL-9, IL-13, IL-17, TNF-α, sCD40L and VEGF-A levels may be adjunctive biomarkers for differential diagnosis of active TB, LTBI, and NTM disease. Assessment of serum sCD40L and M. tb antigen-specific IFN-γ, TNF-α, and IL-2 levels could help predict successful anti-TB treatment in conjunction with M. tb clearance.
authors.affiliation: Department of Microbiology and Institute of Immunology and Immunological Diseases, Brain Korea 21 Plus Project for the Medical Sciences, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Yun-Gyoung
authors.initials: YG
authors.lastname: Hur
authors.affiliation: Division of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Young Ae
authors.initials: YA
authors.lastname: Kang
authors.affiliation: Division of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Jang
authors.affiliation: Division of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Hong
authors.affiliation: Department of Microbiology and Institute of Immunology and Immunological Diseases, Brain Korea 21 Plus Project for the Medical Sciences, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Ahreum
authors.initials: A
authors.lastname: Kim
authors.affiliation: Division of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Sang A
authors.initials: SA
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Institute of Immunology and Immunological Diseases, Brain Korea 21 Plus Project for the Medical Sciences, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Youngmi
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Institute of Immunology and Immunological Diseases, Brain Korea 21 Plus Project for the Medical Sciences, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea. Electronic address: raycho@yuhs.ac.
authors.forename: Sang-Nae
authors.initials: SN
authors.lastname: Cho
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood*; D054357:Chemokine CXCL10 / Q000097:blood; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007159:Immunologic Tests; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2; D055985:Latent Tuberculosis / Q000175:diagnosis* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009165:Mycobacterium Infections, Nontuberculous / Q000175:diagnosis*; D011933:Reagent Kits, Diagnostic; D014374:Tuberculin Test; D014376:Tuberculosis / Q000175:diagnosis* / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D015415:Biomarkers; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D016207:Cytokines; D007376:Interleukin-2; D011933:Reagent Kits, Diagnostic; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D007371:Interferon-gamma
keywords: Biomarker; Diagnosis; Latent tuberculosis infection (LTBI); Mycobacterium tuberculosis (M. tb); Nontuberculous mycobacteria (NTM); Treatment; Tuberculosis (TB)