VPREB3 and Immunodeficiency: In connection with the upregulation of multiple inhibitory pathways, genes significantly downregulated in both adult and childhood TB were predominantly enriched with pathways including chemokine receptor binding, Ca2+ signaling, B-cell (CD79A and B, BLR1, EBI2, VPREB3, ID3, FCRLA, FAIM3, FCGBP, CCR7) and T-cell (BACH2, CD6, CD5, BCL11B, TCL1A, TCF7, CCR7, LEF1), and T/NK cell functions that showed significant suppression of the CD3 zeta (CD247)-EPHA4/NCR3 axis, CD96, UBASH3A, GZMK, and critically IL7R that when suppressed leads to severe immunodeficiency (Figure 4A).