Distinct blood transcriptomic signature of treatment in latent tuberculosis infected individuals at risk of developing active disease

Julie G Burel; Akul Singhania; Paige Dubelko; Julius Muller; Rachel Tanner; Eneida Parizotto; Martin Dedicoat; Thomas E. Fletcher; James Dunbar; Adam F Cunningham; Cecilia S. Lindestam Arlehamn; Donald G. Catanzaro; Antonino Catanzaro; Timothy Rodwell; Helen McShane; Matthew K O'Shea; Bjoern Peters

doi:10.1016/j.tube.2021.102127

Distinct blood transcriptomic signature of treatment in latent tuberculosis infected individuals at risk of developing active disease

Julie G Burel, Akul Singhania, Paige Dubelko, Julius Muller, Rachel Tanner, Eneida Parizotto, Martin Dedicoat, Thomas E. Fletcher, James Dunbar, Adam F Cunningham, Cecilia S. Lindestam Arlehamn, Donald G. Catanzaro, Antonino Catanzaro, Timothy Rodwell, Helen McShane, Matthew K O'Shea^*, Bjoern Peters^*

^*Corresponding author for this work

Immunology and Immunotherapy

Research output: Contribution to journal › Article › peer-review

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Abstract

Although only a small fraction will ever develop the active form of tuberculosis (ATB) disease, chemoprophylaxis treatment in latent TB infected (LTBI) individuals is an effective strategy to control pathogen transmission. Characterizing immune responses in LTBI upon chemoprophylactic treatment is important to facilitate treatment monitoring, and thus improve TB control strategies. Here, we studied changes in the blood transcriptome in a cohort of 42 LTBI and 8 ATB participants who received anti-TB therapy. Based on the expression of previously published gene signatures of progression to ATB, we stratified the LTBI cohort in two groups and examined if individuals deemed to be at elevated risk of developing ATB before treatment (LTBI-Risk) differed from others (LTBI-Other). We found that LTBI-Risk and LTBI-Other groups were associated with two distinct transcriptomic treatment signatures, with the LTBI-Risk signature resembling that of treated ATB patients. Notably, overlapping genes between LTBI-Risk and ATB treatment signatures were associated with risk of progression to ATB and interferon (IFN) signaling, and were selectively downregulated upon treatment in the LTBI-Risk but not the LTBI-Other group. Our results suggest that transcriptomic reprogramming following treatment of LTBI is heterogeneous and can be used to distinguish LTBI-Risk individuals from the LTBI cohort at large.

Original language	English
Article number	102127
Number of pages	11
Journal	Tuberculosis
Volume	131
Early online date	14 Sept 2021
DOIs	https://doi.org/10.1016/j.tube.2021.102127
Publication status	Published - Dec 2021

Bibliographical note

Funding:
This work was funded by the Wellcome Trust (grant number 103420/Z/13/Z), the British Lung Foundation (grant number BHPG13-2), and the National Institute of Allergy and Infectious Diseases of the National Institute of Health (grant numbers R01 AI137681 and U19 AI118626). The funders were not involved in study design, data collection and analysis, decision to publish, nor in preparation of the manuscript. C. Broderick et al.

Copyright:
© 2021 The Authors. Published by Elsevier Ltd.

Keywords

Adult
Case-Control Studies
England
Female
Gene Expression Profiling/methods
Humans
Latent Tuberculosis/blood
Longitudinal Studies
Male
Middle Aged
Mycobacterium tuberculosis/drug effects
State Medicine/organization & administration
Tissue Array Analysis/methods
Transcriptome/genetics

UN SDGs

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

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10.1016/j.tube.2021.102127Licence: Creative Commons: Attribution-NonCommercial-NoDerivs (CC BY-NC-ND)

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Burel, J. G., Singhania, A., Dubelko, P., Muller, J., Tanner, R., Parizotto, E., Dedicoat, M., Fletcher, T. E., Dunbar, J., Cunningham, A. F., Lindestam Arlehamn, C. S., Catanzaro, D. G., Catanzaro, A., Rodwell, T., McShane, H., O'Shea, M. K., & Peters, B. (2021). Distinct blood transcriptomic signature of treatment in latent tuberculosis infected individuals at risk of developing active disease. Tuberculosis, 131, Article 102127. https://doi.org/10.1016/j.tube.2021.102127

@article{82cd15b24cfb4fbfb03cb46c5c07d69c,

title = "Distinct blood transcriptomic signature of treatment in latent tuberculosis infected individuals at risk of developing active disease",

abstract = "Although only a small fraction will ever develop the active form of tuberculosis (ATB) disease, chemoprophylaxis treatment in latent TB infected (LTBI) individuals is an effective strategy to control pathogen transmission. Characterizing immune responses in LTBI upon chemoprophylactic treatment is important to facilitate treatment monitoring, and thus improve TB control strategies. Here, we studied changes in the blood transcriptome in a cohort of 42 LTBI and 8 ATB participants who received anti-TB therapy. Based on the expression of previously published gene signatures of progression to ATB, we stratified the LTBI cohort in two groups and examined if individuals deemed to be at elevated risk of developing ATB before treatment (LTBI-Risk) differed from others (LTBI-Other). We found that LTBI-Risk and LTBI-Other groups were associated with two distinct transcriptomic treatment signatures, with the LTBI-Risk signature resembling that of treated ATB patients. Notably, overlapping genes between LTBI-Risk and ATB treatment signatures were associated with risk of progression to ATB and interferon (IFN) signaling, and were selectively downregulated upon treatment in the LTBI-Risk but not the LTBI-Other group. Our results suggest that transcriptomic reprogramming following treatment of LTBI is heterogeneous and can be used to distinguish LTBI-Risk individuals from the LTBI cohort at large.",

keywords = "Adult, Case-Control Studies, England, Female, Gene Expression Profiling/methods, Humans, Latent Tuberculosis/blood, Longitudinal Studies, Male, Middle Aged, Mycobacterium tuberculosis/drug effects, State Medicine/organization & administration, Tissue Array Analysis/methods, Transcriptome/genetics",

author = "Burel, {Julie G} and Akul Singhania and Paige Dubelko and Julius Muller and Rachel Tanner and Eneida Parizotto and Martin Dedicoat and Fletcher, {Thomas E.} and James Dunbar and Cunningham, {Adam F} and {Lindestam Arlehamn}, {Cecilia S.} and Catanzaro, {Donald G.} and Antonino Catanzaro and Timothy Rodwell and Helen McShane and O'Shea, {Matthew K} and Bjoern Peters",

note = "Funding: This work was funded by the Wellcome Trust (grant number 103420/Z/13/Z), the British Lung Foundation (grant number BHPG13-2), and the National Institute of Allergy and Infectious Diseases of the National Institute of Health (grant numbers R01 AI137681 and U19 AI118626). The funders were not involved in study design, data collection and analysis, decision to publish, nor in preparation of the manuscript. C. Broderick et al. Copyright: {\textcopyright} 2021 The Authors. Published by Elsevier Ltd.",

year = "2021",

month = dec,

doi = "10.1016/j.tube.2021.102127",

language = "English",

volume = "131",

journal = "Tuberculosis",

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Burel, JG, Singhania, A, Dubelko, P, Muller, J, Tanner, R, Parizotto, E, Dedicoat, M, Fletcher, TE, Dunbar, J, Cunningham, AF, Lindestam Arlehamn, CS, Catanzaro, DG, Catanzaro, A, Rodwell, T, McShane, H, O'Shea, MK & Peters, B 2021, 'Distinct blood transcriptomic signature of treatment in latent tuberculosis infected individuals at risk of developing active disease', Tuberculosis, vol. 131, 102127. https://doi.org/10.1016/j.tube.2021.102127

TY - JOUR

T1 - Distinct blood transcriptomic signature of treatment in latent tuberculosis infected individuals at risk of developing active disease

AU - Burel, Julie G

AU - Singhania, Akul

AU - Dubelko, Paige

AU - Muller, Julius

AU - Tanner, Rachel

AU - Parizotto, Eneida

AU - Dedicoat, Martin

AU - Fletcher, Thomas E.

AU - Dunbar, James

AU - Cunningham, Adam F

AU - Lindestam Arlehamn, Cecilia S.

AU - Catanzaro, Donald G.

AU - Catanzaro, Antonino

AU - Rodwell, Timothy

AU - McShane, Helen

AU - O'Shea, Matthew K

AU - Peters, Bjoern

N1 - Funding: This work was funded by the Wellcome Trust (grant number 103420/Z/13/Z), the British Lung Foundation (grant number BHPG13-2), and the National Institute of Allergy and Infectious Diseases of the National Institute of Health (grant numbers R01 AI137681 and U19 AI118626). The funders were not involved in study design, data collection and analysis, decision to publish, nor in preparation of the manuscript. C. Broderick et al. Copyright: © 2021 The Authors. Published by Elsevier Ltd.

PY - 2021/12

Y1 - 2021/12

N2 - Although only a small fraction will ever develop the active form of tuberculosis (ATB) disease, chemoprophylaxis treatment in latent TB infected (LTBI) individuals is an effective strategy to control pathogen transmission. Characterizing immune responses in LTBI upon chemoprophylactic treatment is important to facilitate treatment monitoring, and thus improve TB control strategies. Here, we studied changes in the blood transcriptome in a cohort of 42 LTBI and 8 ATB participants who received anti-TB therapy. Based on the expression of previously published gene signatures of progression to ATB, we stratified the LTBI cohort in two groups and examined if individuals deemed to be at elevated risk of developing ATB before treatment (LTBI-Risk) differed from others (LTBI-Other). We found that LTBI-Risk and LTBI-Other groups were associated with two distinct transcriptomic treatment signatures, with the LTBI-Risk signature resembling that of treated ATB patients. Notably, overlapping genes between LTBI-Risk and ATB treatment signatures were associated with risk of progression to ATB and interferon (IFN) signaling, and were selectively downregulated upon treatment in the LTBI-Risk but not the LTBI-Other group. Our results suggest that transcriptomic reprogramming following treatment of LTBI is heterogeneous and can be used to distinguish LTBI-Risk individuals from the LTBI cohort at large.

AB - Although only a small fraction will ever develop the active form of tuberculosis (ATB) disease, chemoprophylaxis treatment in latent TB infected (LTBI) individuals is an effective strategy to control pathogen transmission. Characterizing immune responses in LTBI upon chemoprophylactic treatment is important to facilitate treatment monitoring, and thus improve TB control strategies. Here, we studied changes in the blood transcriptome in a cohort of 42 LTBI and 8 ATB participants who received anti-TB therapy. Based on the expression of previously published gene signatures of progression to ATB, we stratified the LTBI cohort in two groups and examined if individuals deemed to be at elevated risk of developing ATB before treatment (LTBI-Risk) differed from others (LTBI-Other). We found that LTBI-Risk and LTBI-Other groups were associated with two distinct transcriptomic treatment signatures, with the LTBI-Risk signature resembling that of treated ATB patients. Notably, overlapping genes between LTBI-Risk and ATB treatment signatures were associated with risk of progression to ATB and interferon (IFN) signaling, and were selectively downregulated upon treatment in the LTBI-Risk but not the LTBI-Other group. Our results suggest that transcriptomic reprogramming following treatment of LTBI is heterogeneous and can be used to distinguish LTBI-Risk individuals from the LTBI cohort at large.

KW - Adult

KW - Case-Control Studies

KW - England

KW - Female

KW - Gene Expression Profiling/methods

KW - Humans

KW - Latent Tuberculosis/blood

KW - Longitudinal Studies

KW - Male

KW - Middle Aged

KW - Mycobacterium tuberculosis/drug effects

KW - State Medicine/organization & administration

KW - Tissue Array Analysis/methods

KW - Transcriptome/genetics

U2 - 10.1016/j.tube.2021.102127

DO - 10.1016/j.tube.2021.102127

M3 - Article

C2 - 34555657

SN - 1472-9792

VL - 131

JO - Tuberculosis

JF - Tuberculosis

M1 - 102127

ER -

Distinct blood transcriptomic signature of treatment in latent tuberculosis infected individuals at risk of developing active disease

Abstract

Bibliographical note

Keywords

UN SDGs

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