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

S Dhanasekaran; S Jenum; R Stavrum; Christian Ritz; Daniel Faurholt-Jepsen; J Kenneth; M Vaz; H M S Grewal; T M Doherty; TB Trials Study Group

doi:10.1038/gene.2013.26

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

S Dhanasekaran, S Jenum, R Stavrum, Christian Ritz, Daniel Faurholt-Jepsen, J Kenneth, M Vaz, H M S Grewal, T M Doherty, TB Trials Study Group

Lifecourse Nutrition & Health

29 Citations (Scopus)

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.

Original language	English
Journal	Genes and Immunity
Volume	14
Issue number	6
Pages (from-to)	356-364
Number of pages	9
ISSN	1466-4879
DOIs	https://doi.org/10.1038/gene.2013.26
Publication status	Published - Sept 2013

Keywords

Antigens, CD4
BCG Vaccine
Biological Markers
Carrier Proteins
Case-Control Studies
Chemokine CXCL10
Child, Preschool
Female
Forkhead Transcription Factors
Humans
India
Infant
Infant, Newborn
Interleukin-13
Interleukin-2
Male
RNA, Messenger
Receptors, Tumor Necrosis Factor, Type I
Transforming Growth Factor beta1
Tuberculosis
rab GTP-Binding Proteins

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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https://www.nature.com/articles/gene201326.pdf

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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.",

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author = "S Dhanasekaran and S Jenum and R Stavrum and Christian Ritz and Daniel Faurholt-Jepsen and J Kenneth and M Vaz and Grewal, {H M S} and Doherty, {T M} and {TB Trials Study Group}",

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T1 - Identification of biomarkers for Mycobacterium tuberculosis infection and disease in BCG-vaccinated young children in Southern India

AU - Dhanasekaran, S

AU - Jenum, S

AU - Stavrum, R

AU - Ritz, Christian

AU - Faurholt-Jepsen, Daniel

AU - Kenneth, J

AU - Vaz, M

AU - Grewal, H M S

AU - Doherty, T M

AU - TB Trials Study Group

N1 - CURIS 2013 NEXS 230

PY - 2013/9

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N2 - 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.

AB - 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.

KW - Antigens, CD4

KW - BCG Vaccine

KW - Biological Markers

KW - Carrier Proteins

KW - Case-Control Studies

KW - Chemokine CXCL10

KW - Child, Preschool

KW - Female

KW - Forkhead Transcription Factors

KW - Humans

KW - India

KW - Infant

KW - Infant, Newborn

KW - Interleukin-13

KW - Interleukin-2

KW - Male

KW - RNA, Messenger

KW - Receptors, Tumor Necrosis Factor, Type I

KW - Transforming Growth Factor beta1

KW - Tuberculosis

KW - rab GTP-Binding Proteins

U2 - 10.1038/gene.2013.26

DO - 10.1038/gene.2013.26

M3 - Journal article

C2 - 23676757

SN - 1466-4879

VL - 14

SP - 356

EP - 364

JO - Genes and Immunity

JF - Genes and Immunity

IS - 6

ER -

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

Abstract

Keywords

UN SDGs

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