title: Effect of non-tuberculous Mycobacteria on host biomarkers potentially relevant for tuberculosis management.
abstract: BACKGROUND
  Non-tuberculous mycobacteria (NTM) are different from Mycobacterium tuberculosis (MTB) both in their ubiquitous environmental distribution and in their reduced capacity to cause disease. While often neglected in favour of other infectious diseases, NTM may interfere with important aspects of TB control and management, namely the efficacy of new anti-tuberculosis (TB) vaccines; the immuno-diagnostic Tuberculin skin test (TST) and QuantiFERON TB Gold In Tube assay (QFTGIT); and immune biomarkers explored for their diagnostic and/or predictive potential. Our objective was therefore to explore host immune biomarkers in children who had NTM isolated from respiratory and/or gastric specimens.
  
  
  RESULTS
  The present study was nested within a prospective cohort study of BCG-vaccinated neonates in Southern India. In this setting, immune biomarkers from peripheral blood were analyzed in 210 children aged <3 years evaluated for TB using dual-colour-Reverse-Transcriptase-Multiple-Ligation-dependent-Probe-Amplification (dcRT-MLPA) and Bio-Plex assays. The children were classified based on clinical examination, chest X-rays and mycobacterial culture reports as either: 1) TB disease, 2) NTM present and 3) controls. The study shows a down-regulation of RAB33A (p<0.001) and up-regulation of TGFβ1, IL-2 and IL-6 (all p<0.05) in children with TB disease, and that RAB33A, TGFBR2 and IL-10 (all p<0.05) were differentially expressed in children with NTM present when compared to children that were culture negative for MTB and NTM (controls).
  
  
  CONCLUSIONS
  Carriage of NTM may reduce the specificity of future diagnostic and predictive immune biomarkers relevant to TB management.
authors.affiliation: Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
authors.forename: S
authors.initials: S
authors.lastname: Dhanasekaran
authors.affiliation: Center for Immune Regulation, Rikshospitalet- Radium Hospitalet Medical Centre, University of Oslo, Oslo, Norway.
authors.forename: Synne
authors.initials: S
authors.lastname: Jenum
authors.affiliation: Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
authors.forename: Ruth
authors.initials: R
authors.lastname: Stavrum
authors.affiliation: Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
authors.forename: Harald G
authors.initials: HG
authors.lastname: Wiker
authors.affiliation: Division of Infectious Diseases, St. John's Research Institute, Koramangala, Bangalore, India.
authors.forename: John
authors.initials: J
authors.lastname: Kenneth
authors.affiliation: Division of Health & Humanities, St. John's Research Institute, Koramangala, Bangalore, India.
authors.forename: Mario
authors.initials: M
authors.lastname: Vaz
authors.affiliation: Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway; GlaxoSmithKline Pharma, Vaccines, Brøndby, Denmark.
authors.forename: T Mark
authors.initials: TM
authors.lastname: Doherty
authors.affiliation: Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway; Department of Microbiology, Haukeland university hospital, University of Bergen, Bergen, Norway.
authors.forename: Harleen M S
authors.initials: HM
authors.lastname: Grewal
mesh_terms: D001500:BCG Vaccine / Q000276:immunology*; D015415:Biomarkers / Q000097:blood*; D002675:Child, Preschool; D015331:Cohort Studies; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007194:India; D007223:Infant; D007231:Infant, Newborn; D016753:Interleukin-10 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology; D009170:Nontuberculous Mycobacteria / Q000276:immunology* / Q000302:isolation & purification; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis; D014374:Tuberculin Test; D014376:Tuberculosis / Q000175:diagnosis* / Q000382:microbiology / Q000628:therapy; D015854:Up-Regulation; D020691:rab GTP-Binding Proteins / Q000096:biosynthesis
chemical_list: D001500:BCG Vaccine; D015415:Biomarkers; C508609:IL10 protein, human; C508594:IL2 protein, human; C508600:IL6 protein, human; D007376:Interleukin-2; D015850:Interleukin-6; C105244:RAB33A protein, human; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D020691:rab GTP-Binding Proteins