Whole-Blood Transcriptomic Profiling of Active and Latent Tuberculosis in Patients in Kaduna State: Identifying Diagnostic Biosignatures for Nigerian Populations

Host blood transcriptomic signatures offer a promising avenue for developing rapid molecular diagnostics that can differentiate active tuberculosis from latent infection, a challenge that conventional tests cannot adequately address. This study investigated whole-blood gene expression profiles in active tuberculosis, latent tuberculosis infection, and healthy controls among participants in Kaduna State, North West Nigeria. A case-control design enrolled 30 bacteriologically confirmed active TB patients, 30 QuantiFERON-TB positive LTBI individuals, and 30 healthy uninfected controls. Whole-blood PAXgene RNA was extracted and profiled using Affymetrix microarrays. Differential expression analysis, gene ontology enrichment, and receiver operating characteristic analysis for candidate biomarker signatures were performed. A 20-gene biosignature predominantly composed of interferon-stimulated genes and neutrophil-related transcripts distinguished active TB from LTBI with area under the curve of 0.91. Active TB versus healthy control discrimination had AUC of 0.97. Several genes in the signature overlapped with previously described multi-country signatures, validating cross-population applicability. Novel candidate genes with no prior TB association were identified, warranting further functional characterisation. The LTBI versus healthy control comparison yielded modest separation, highlighting the diagnostic gap in latent disease. The study provides preliminary evidence for a Nigerian-specific transcriptomic TB biosignature and recommends validation in larger multi-site cohorts across Nigeria's geopolitical zones before platform-specific translation for point-of-care application. Keywords: transcriptomics, tuberculosis, biosignature, interferon-stimulated genes, latent tuberculosis