Assessing tuberculosis risk in pregnant women from the PRACHITi study using transcriptomics

A new tuberculosis (TB) diagnostic cartridge assay, which detects a 3-gene TB signature in whole blood, was not diagnostic in women with maternal TB disease in India (area under the curve [AUC] = 0.72). In a cohort of pregnant women, we identified a novel gene set for TB diagnosis (AUC = 0.97) and one for TB progression (AUC = 0.96).

The highest-risk time for a woman to develop tuberculosis (TB) disease is within 90 days postpartum [1], likely related to suppression of cell-mediated immunity during pregnancy followed by relative immune reconstitution immediately postpartum [2]. These changes can mask TB symptoms, causing underdiagnosis peripartum. A test that reliably diagnoses maternal TB would decrease TB-related complications for mother and child.

Transcriptional RNA signatures are blood-based tests that diagnose TB disease or predict progression from TB infection to disease [3]. Of 47 published transcriptional TB studies, none included pregnant women. Most TB signatures, including the 3-gene signature developed into a cartridge-based diagnostic assay [4], identify upregulated inflammatory pathways [3, 4]. Because proinflammatory pathways are suppressed during pregnancy [2], TB signatures in nonpregnant populations may not be valid during pregnancy and postpartum.

We sought to identify differentially expressed genes (DEGs) in pregnant and postpartum women, before progressing and at TB diagnosis, to determine if published signatures remain valid and to identify differences in TB pathogenesis during pregnancy.