title: BLR1 and FCGR1A transcripts in peripheral blood associate with the extent of intrathoracic tuberculosis in children and predict treatment outcome.
abstract: Biomarkers reflecting the extent of Mycobacterium tuberculosis-induced pathology and normalization during anti-tuberculosis treatment (ATT) would considerably facilitate trials of new treatment regimens and the identification of patients with treatment failure. Therefore, in a cohort of 99 Indian children with intrathoracic tuberculosis (TB), we performed blood transcriptome kinetic analysis during ATT to explore 1) the association between transcriptional biomarkers in whole blood (WB) and the extent of TB disease at diagnosis and treatment outcomes at 2 and 6 months, and 2) the potential of the biomarkers to predict treatment response at 2 and 6 months. We present the first data on the association between transcriptional biomarkers and the extent of TB disease as well as outcome of ATT in children: Expression of three genes down-regulated on ATT (FCGR1A, FPR1 and MMP9) exhibited a positive correlation with the extent of TB disease, whereas expression of eight up-regulated genes (BCL, BLR1, CASP8, CD3E, CD4, CD19, IL7R and TGFBR2) exhibited a negative correlation with the extent of disease. Baseline levels of these transcripts displayed an individual capacity >70% to predict the six-month treatment outcome. In particular, BLR1 and FCGR1A seem to have a potential in monitoring and perhaps tailoring future antituberculosis therapy.
authors.affiliation: Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.|Department of Infectious Diseases, Oslo University Hospital, 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: Rasmus
authors.initials: R
authors.lastname: Bakken
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: Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Aparna
authors.initials: A
authors.lastname: Mukherjee
authors.affiliation: Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Lodha
authors.affiliation: Division of Clinical Microbiology &Molecular Medicine, Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Sarman
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Pediatrics, Kalawati Saran Children Hospital, New Delhi, India.
authors.forename: Varinder
authors.initials: V
authors.lastname: Singh
authors.affiliation: Department of Infectious Diseases Group, Immunology and Immunogenetics of Bacterial Infectious Disease, Leiden University Medical Center, The Netherland.
authors.forename: Marielle C
authors.initials: MC
authors.lastname: Haks
authors.affiliation: Department of Infectious Diseases Group, Immunology and Immunogenetics of Bacterial Infectious Disease, Leiden University Medical Center, The Netherland.
authors.forename: Tom H M
authors.initials: TH
authors.lastname: Ottenhoff
authors.affiliation: Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: S K
authors.initials: SK
authors.lastname: Kabra
authors.affiliation: GlaxoSmithKline Vaccines, Warve, Belgium.
authors.forename: T Mark
authors.initials: TM
authors.lastname: Doherty
authors.affiliation: Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Ritz
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, N-5021, Norway.
authors.forename: Harleen M S
authors.initials: HM
authors.lastname: Grewal
mesh_terms: D000293:Adolescent; D000995:Antitubercular Agents / Q000627:therapeutic use; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004311:Double-Blind Method; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007194:India; D007223:Infant; D008297:Male; D044342:Malnutrition / Q000150:complications / Q000188:drug therapy; D008345:Manganese / Q000627:therapeutic use; D018977:Micronutrients / Q000627:therapeutic use; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000097:blood* / Q000235:genetics; D016032:Randomized Controlled Trials as Topic; D054380:Receptors, CXCR5 / Q000235:genetics*; D017452:Receptors, IgG / Q000235:genetics*; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000097:blood* / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D015032:Zinc / Q000627:therapeutic use
chemical_list: D000995:Antitubercular Agents; D015415:Biomarkers; C095085:CXCR5 protein, human; C489017:FCGR1A protein, human; D018977:Micronutrients; D012333:RNA, Messenger; D054380:Receptors, CXCR5; D017452:Receptors, IgG; D008345:Manganese; D015032:Zinc