A whole-blood transcriptional signature associated with obstructive post-tuberculosis lung disease

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ID: 331987
2026
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Abstract
Abstract Background Post-tuberculosis (TB) lung disease (PTLD) affects approximately 50% of persons with pulmonary TB. 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 naïve adults with newly diagnosed pulmonary TB (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). Findings 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=0.003), 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=0.003) and 12 months (p=0.012) in bivariate and multivariate analyses. The mHR score was not associated with restrictive lung disease. Interpretation 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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Authors Renee E. Newby, Lucy Kijaro, Kimberly A. Dill‐McFarland, Lilian N. Njagi, Wilfred Bundi Murithi, Zipporah Mwongera, Moeko Agata, Jodi Byers, Glenna J. Peterson, Kevin P. Fennelly, Videlis Nduba, David J. de L. Horne, Jerry S. Zifodya, Thomas R. Hawn
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Journal Open forum infectious diseases
Year 2026
DOI
10.1093/ofid/ofag610
URL
https://doi.org/10.1093/ofid/ofag610
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