Fig. 4

Transcriptional biomarkers and biomarker pathways that drive fatal inflammation during C-IRIS events. These biomarker transcripts were identified using a partial least square algorithm. The pathways that play a role in fatal outcome are depicted in grey boxes. The transcripts that are unique to the Fatal C-IRIS Group are depicted in clear boxes. The pathways shared with the Death without C-IRIS Group are depicted on the left; the pathways shared with the C-IRIS Survivor Group are depicted on the right. Pathways shared by all three groups are depicted on the bottom. Our model suggests that the overactivated innate immune system, driven by monocytes via inflammasome/TLR2,4 pathways, drives C-IRIS events (right). Excessive neutrophil activation via fMLP, Rho family GTPases, HMGB1 and inactive RhoGDI pathways results in cellular and tissue damage promoting the pathogenesis of fatal events (left)