Early tuberculosis treatment remodels blood mRNA and small RNA, and a baseline host signature is associated with early culture conversion

Early tuberculosis treatment induces coordinated remodeling of blood mRNA and small RNA profiles, including 63 concordantly regulated genes and treatment-linked miRNAs/tRFs.

• Why it matters: Sputum-based TB monitoring is slow and limited, so rapid blood biomarkers are needed to reflect host response and treatment progress.
• What they did: Paired whole-blood samples from three South African cohorts were analyzed by integrative multi-omics, with meta-analysis of RNA-seq (GSE89403, n=76; plus 11 pairs) and directional concordance in GSE31348 (27 pairs). A baseline k-top scoring pairs signature (EARLY5) was trained to predict week-4 sputum culture conversion, yielding cross-validated AUC 0.76.
• The result: EARLY5 identified participants who converted by week 4 and remained associated after adjustment for baseline bacterial burden in logistic regression, and baseline host transcriptional profiles were linked to early culture conversion.