Open forum infectious diseases · 2026
A Whole-blood Transcriptional Signature Associated With Obstructive Post-tuberculosis Lung Disease.
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Newby Renee E, Kijaro Lucy, Dill-McFarland Kimberly A, Njagi Lilian N, Murithi Wilfred B, Mwongera Zipporah, Agata Moeko, Byers Jodi, Peterson Glenna J, Fennelly Kevin P, Nduba Videlis, Horne David J, Zifodya Jerry S, Hawn Thomas R
Аннотация
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.
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.