title: Identification of biomarkers for Mycobacterium tuberculosis infection and disease in BCG-vaccinated young children in Southern India.
abstract: Pediatric tuberculosis (TB) often goes undiagnosed because of the lack of reliable diagnostic methods. With the aim of assessing biomarker(s) that can aid in the diagnosis of TB infection and disease, we investigated 746 Indian children with suspected TB. Whole-blood mRNA from 210 children was examined by dual-color Reverse-Transcriptase Multiple Ligation-dependent Probe-Amplification for the expression of 45 genes and a Bio-Plex assay for the expression of cytokines/chemokines in QuantiFERON supernatants. The study shows that transcription of SEC14L1, GUSB, BPI, CCR7 and TGFβ-1 (all P ≤ 0.05) was downregulated in TB disease compared with uninfected controls, while transcription of RAB33A was downregulated in TB disease compared with both latent TB (P < 0.05) and controls (P < 0.01). The transcription of CD4, TGFβ-1 (P < 0.01) and the expression of IL-2 (P < 0.01) and IL-13 (P < 0.05) was upregulated in latent TB compared with that in controls. Using the Least Absolute Shrinkage and Selection Operator (lasso) model, RAB33A alone discriminated between TB disease and latent TB (area under the curve (AUC) 77.5%), whereas a combination of RAB33A, CXCL10, SEC14L1, FOXP3 and TNFRSF1A was effective in discriminating between TB disease and controls (AUC 91.7%). A combination of 11 biomarkers predicted latent TB with moderate discriminatory power (AUC 72.2%). In conclusion, RAB33A is a potential biomarker for TB disease, whereas CD4, TGFβ-1 and IL-2, IL-13 may identify latent TB in children.
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.forename: S
authors.initials: S
authors.lastname: Jenum
authors.forename: R
authors.initials: R
authors.lastname: Stavrum
authors.forename: C
authors.initials: C
authors.lastname: Ritz
authors.forename: D
authors.initials: D
authors.lastname: Faurholt-Jepsen
authors.forename: J
authors.initials: J
authors.lastname: Kenneth
authors.forename: M
authors.initials: M
authors.lastname: Vaz
authors.forename: H M S
authors.initials: HM
authors.lastname: Grewal
authors.forename: T M
authors.initials: TM
authors.lastname: Doherty
mesh_terms: D001500:BCG Vaccine / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism; D002675:Child, Preschool; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007194:India; D007223:Infant; D007231:Infant, Newborn; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism*; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D014376:Tuberculosis / Q000175:diagnosis* / Q000378:metabolism / Q000517:prevention & control; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D001500:BCG Vaccine; D015415:Biomarkers; D015704:CD4 Antigens; C114753:CXCL10 protein, human; D002352:Carrier Proteins; D054357:Chemokine CXCL10; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C578095:IL13 protein, human; C508594:IL2 protein, human; D018793:Interleukin-13; D007376:Interleukin-2; C105244:RAB33A protein, human; D012333:RNA, Messenger; D047888:Receptors, Tumor Necrosis Factor, Type I; C100642:SEC14L1 protein, human; C506235:TNFRSF1A protein, human; D053773:Transforming Growth Factor beta1; D020691:rab GTP-Binding Proteins