Abstract
BACKGROUND: Latent tuberculosis infection affects about one-quarter of the global population and can progress to active tuberculosis. Hematological inflammatory markers, such as the systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio, reflect systemic inflammation and immune status but are understudied in latent tuberculosis infection. This study investigates the association between these markers and latent tuberculosis infection in a nationally representative sample. METHODS: Data from 7,042 participants in the 2011-2012 National Health and Nutrition Examination Survey and transcriptomic data from the GSE19491 dataset were analyzed. Latent tuberculosis infection was identified using the QuantiFERON-TB Gold assay. Hematological parameters were measured via complete blood counts, and inflammatory markers were calculated through these parameters. Statistical analyses included linear regression adjusted for confounders and subgroup analyses. Transcriptomic analyses involved immune cell profiling, gene set enrichment, and immune checkpoint gene expression. RESULTS: Individuals with latent tuberculosis infection had significantly lower systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio. These associations remained significant after adjusting for age, gender, body mass index, diabetes, and hypertension. Transcriptomic analyses revealed heightened activation of memory CD4 and CD8 T cells, increased cytolytic activity, and upregulated T-cell co-inhibition pathways, alongside differential expression of immune checkpoint genes in individuals with latent tuberculosis infection. CONCLUSIONS: A lower systemic immune-inflammation index and other related hematological inflammatory markers independently correlate with latent tuberculosis infection. These findings underscore the potential significance of hematological inflammatory markers in identifying and understanding latent tuberculosis infection. Further exploration of these markers may enhance diagnostic and therapeutic strategies of tuberculosis.