An RNA signature for tuberculosis risk in pregnant women: a prospective cohort study from Pune, India

Background: Pregnant and postpartum women are at high risk of developing active tuberculosis (TB), but transcriptional TB studies have excluded pregnant women. We identified differentially expressed genes (DEGs) in pregnant women who did and did not progress to active TB. Methods: We followed a cohort of pregnant Indian women with TB infection for one year postpartum, collecting blood at study entry, 6 weeks postpartum and active TB diagnosis. A prospective signature of risk was identified by comparing whole blood RNA sequencing data from women who developed active TB postpartum (cases) with those who remained healthy (controls). Results: We identified 9 cases and matched them to 18 controls by HIV status and gestational age. A gene set of risk was identified: Expression of KCNIP4 > 2.2 log CPM and S1PR4 < 7.3 log CPM indicated a high probability of developing active TB postpartum. SF3B4 (>4.3 log CPM) and PGAM1 (>6.6 log CPM) correctly classified postpartum cases and controls. Both pairs displayed high accuracy (AUC >0.9) and were unique from 36 published TB signatures.Conclusions: We identified two genes that prospectively differentiated pregnant women who developed active TB postpartum from those who did not. If validated, this signature could be useful in targeted TB prevention programs. gene expression analysis in TB/HIV infected women