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

Burel, Julie G., Singhania, Akul, Dubelko, Paige, Muller, Julius, Tanner, Rachel, Parizotto, Eneida, Dedicoat, Martin, Fletcher, Tom, Dunbar, James, Cunningham, Adam F., Lindestam Arlehamn, Cecilia S., Catanzaro, Donald G., Catanzaro, Antonino, Rodwell, Timothy, McShane, Helen, O'Shea, Matthew K. and Peters, Bjoern (2021) 'Distinct blood transcriptomic signature of treatment in latent tuberculosis infected individuals at risk of developing active disease'. Tuberculosis, Vol 131, p. 102127.

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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.

Item Type:	Article
Subjects:	QU Biochemistry > Genetics > QU 450 General Works QY Clinical Pathology > Blood. Blood Chemistry > QY 450 Blood chemistry WF Respiratory System > Tuberculosis > WF 200 Tuberculosis (General) WF Respiratory System > Tuberculosis > WF 215 Pathology
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1016/j.tube.2021.102127
Depositing User:	Marie Hatton
Date Deposited:	11 Jan 2022 12:30
Last Modified:	16 Jun 2023 09:53
URI:	https://archive.lstmed.ac.uk/id/eprint/19677

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