Transcriptional signatures of human peripheral blood mononuclear cells can identify the risk of tuberculosis progression from latent infection among individuals with silicosis

Abstract

Host immune factor plays an important role in the progression of latent tuberculosis infection (LTBI) to active tuberculosis (TB) disease. However, whether global gene expression measured in blood biomarkers allows the identification of prospective signatures for TB risk remains unknown. Hence, we aimed to assess the ability of the transcriptome signatures in the human peripheral blood mononuclear cells (PBMCs) of LTBI subjects to differentiate future TB progressors from non-progressors. In a randomized clinical trial of TB preventive treatment of 513 participants with silicosis, we randomly collected PBMC samples from 50 LTBI subjects in the observational group, which was monitored for TB disease progression for 37 months. The prospective signatures of TB risk between the two participants who developed active TB (progressors) and four matched individuals who remained healthy (non-progressors) were compared using differential expression analysis, Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and Weighted Gene Co-expression Network Analysis. The 20 TB-specific differentially expressed genes, which were significantly downregulated in TB progressors, were revealed to be associated with interferon-gamma response-related genes. Therefore, the PBMC transcriptome profiles analyzed in this study may help identify LTBI individuals who are at risk of progressing to active TB among silicosis patients and may provide new insights for targeted intervention to prevent disease progression.Clinical trial registration www.clinicaltrials.gov (NCT02430259)

Keywords

• Tuberculosis
• peripheral blood mononuclear cell
• biomarker
• latent tuberculosis infection
• RNA sequencing
• interferon-gamma