A Whole-blood Transcriptional Signature Associated With Obstructive Post-tuberculosis Lung Disease.
5 affiliations
- 1Department of Medicine, University of Washington, Seattle, Washington, USA.
- 2Centre for Respiratory Diseases Research, Kenya Medical Research Institute, Nairobi, Kenya.
- 3Department of Global Health, University of Washington, Seattle, Washington, USA.
- 4Division of Intramural Research, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health, Bethesda, Maryland, USA.
- 5Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA.
Abstract
Background
Post-tuberculosis (TB) lung disease (PTLD) affects ∼50% of persons with pulmonary TB (PTB). We recently discovered whole blood transcriptional signatures associated with PTLD. We examined whether a minimum gene signature predicts PTLD as a clinically useful biomarker.Methods
We prospectively enrolled 301 treatment naive adults with newly diagnosed PTB (cohort A). We collected whole blood at 0 and 6-month visits, isolated RNA, and measured a modified MTB host response (HR) signature (mHR) based on expression of DUSP3, GBP5, and TMBIM6. We recorded spirometry at 6 (n = 216) and 12 months (n = 210) after treatment initiation and examined the association of the mHR score with PTLD and Mtb aerosolization. We recruited household contacts of cohort A to compare mHR score with non-PTB participants (cohort B).Results
mHR was associated with TB (P = 4.15e-66) when compared to HHCs, treatment response (P = 1.07e-53), and characteristics including CD4 count (P = .003), bacillary load (P = 3.02e-05), lung cavities (P = 1.59e-04), and lung quadrants involved (P = 3.87e-06). The mHR score was not associated with Mtb aerosolization. In total, 105 (50%) participants had PTLD at 12 months including 61 with restriction, 26 with obstruction, and 18 with mixed obstruction and restriction. Baseline mHR was associated with obstructive PTLD at both 6 (P = .003) and 12 months (P = .012) in bivariate and multivariate analyses. The mHR score was not associated with restrictive lung disease.Conclusions
Baseline mHR was associated with obstructive PTLD at 6 and 12 months and may have applications in targeting treatment and prognostication.
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BibTeX
@article{newby2026wholeblood,
title = {{A Whole-blood Transcriptional Signature Associated With Obstructive Post-tuberculosis Lung Disease.}},
author = {Renee E Newby and Lucy Kijaro and Kimberly A Dill-McFarland and Lilian N Njagi and Wilfred B Murithi and Zipporah Mwongera and Moeko Agata and Jodi Byers and Glenna J Peterson and Kevin P Fennelly and Videlis Nduba and David J Horne and Jerry S Zifodya and Thomas R Hawn},
journal = {Open forum infectious diseases},
year = {2026},
month = oct,
doi = {10.1093/ofid/ofag610},
url = {https://europepmc.org/article/MED/42898833},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - A Whole-blood Transcriptional Signature Associated With Obstructive Post-tuberculosis Lung Disease.
AU - Renee E Newby
AU - Lucy Kijaro
AU - Kimberly A Dill-McFarland
AU - Lilian N Njagi
AU - Wilfred B Murithi
AU - Zipporah Mwongera
AU - Moeko Agata
AU - Jodi Byers
AU - Glenna J Peterson
AU - Kevin P Fennelly
AU - Videlis Nduba
AU - David J Horne
AU - Jerry S Zifodya
AU - Thomas R Hawn
PY - 2026
DA - 2026/10/09
JO - Open forum infectious diseases
DO - 10.1093/ofid/ofag610
UR - https://europepmc.org/article/MED/42898833
AB - Background Post-tuberculosis (TB) lung disease (PTLD) affects ∼50% of persons with pulmonary TB (PTB). We recently discovered whole blood transcriptional signatures associated with PTLD. We examined whether a minimum gene signature predicts PTLD as a clinically useful biomarker.Methods We prospectively enrolled 301 treatment naive adults with newly diagnosed PTB (cohort A). We collected whole blood at 0 and 6-month visits, isolated RNA, and measured a modified MTB host response (HR) signature (mHR) based on expression of DUSP3, GBP5, and TMBIM6. We recorded spirometry at 6 (n = 216) and 12 months (n = 210) after treatment initiation and examined the association of the mHR score with PTLD and Mtb aerosolization. We recruited household contacts of cohort A to compare mHR score with non-PTB participants (cohort B).Results mHR was associated with TB (P = 4.15e-66) when compared to HHCs, treatment response (P = 1.07e-53), and characteristics including CD4 count (P = .003), bacillary load (P = 3.02e-05), lung cavities (P = 1.59e-04), and lung quadrants involved (P = 3.87e-06). The mHR score was not associated with Mtb aerosolization. In total, 105 (50%) participants had PTLD at 12 months including 61 with restriction, 26 with obstruction, and 18 with mixed obstruction and restriction. Baseline mHR was associated with obstructive PTLD at both 6 (P = .003) and 12 months (P = .012) in bivariate and multivariate analyses. The mHR score was not associated with restrictive lung disease.Conclusions Baseline mHR was associated with obstructive PTLD at 6 and 12 months and may have applications in targeting treatment and prognostication.
SN - 2328-8957
ER -