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Identification of biomarkers for Mycobacterium tuberculosis infection and disease in BCG-vaccinated young children in Southern India

Genes & Immunity volume 14, pages 356–364 (2013)Cite this article

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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.

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Acknowledgements

We thank Harald G Wiker (University of Bergen) for constructive advice; Aud Eliassen at the sequencing laboratory at Haukeland University Hospital, Bergen, Norway. Diana Mahelai, Geojith George, Sumithra Selvan, Nelson Jesuraj and Naveen Kumar Kellengere at St John’s Research Institute, Bangalore; Lien M Diep (University of Oslo) for technical and statistical assistance. This study is conducted as part of the Indo-Norway research program. This study was supported by the Research Council of Norway (grants 179342, 192534 and 196362), University of Bergen, Aeras USA, and St John’s Research Institute, India.

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Authors and Affiliations

  1. Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway

    S Dhanasekaran, R Stavrum, H M S Grewal & T M Doherty

  2. Center for Immune Regulation, Rikshospitalet–Radium Hospitalet Medical Centre, University of Oslo, Oslo, Norway

    S Jenum

  3. Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark

    C Ritz & D Faurholt-Jepsen

  4. Division of Infectious Diseases, St John’s Research Institute, Bangalore, India

    J Kenneth

  5. Division of Health and Humanities, St John’s Research Institute, Bangalore, India

    M Vaz

  6. Department of Microbiology, Haukeland University Hospital, University of Bergen, Bergen, Norway

    H M S Grewal

  7. GlaxoSmithKline Pharma, Vaccines, Copenhagen, Denmark

    T M Doherty

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TB Trials Study Group

  • M Doherty
  • , H M S Grewal
  • , A C Hesseling
  • , A Jacob
  • , F Jahnsen
  • , J Kenneth
  • , A V Kurpad
  • , B Lindtjorn
  • , R Macaden
  • , J Nelson
  • , S Sumithra
  • , M Vaz
  •  & R Walker

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Correspondence to H M S Grewal.

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Contributors Doherty M, Grewal HMS, Hesseling AC, Jacob A, Jahnsen F, Kenneth J, Kurpad AV, Lindtjorn B, Macaden R, Nelson J, Sumithra S, Vaz M, Walker R

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Dhanasekaran, S., Jenum, S., Stavrum, R. et al. Identification of biomarkers for Mycobacterium tuberculosis infection and disease in BCG-vaccinated young children in Southern India. Genes Immun 14, 356–364 (2013). https://doi.org/10.1038/gene.2013.26

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