Fig. 5

Transcriptomic validation of cytokine signaling pathways and prednisolone response in an independent cohort of PLHTLV-1. Digital transcriptomics (nCounter) was used to quantify cytokine signaling pathways in HAM/TSP disease progression, and the effect of in vitro prednisolone treatment in PBMCs from four AS, four HAM/TSP patients (including the two only incident HAM/TSP in the HOST cohort), and four age-, gender- and ethnicity-matched healthy controls. A Ex vivo IFN signaling score was significantly higher in incident HAM/TSP as compared to healthy controls, AS, and HAM/TSP at 4-year follow-up (one sample t test). B Ex vivo IL-17 signaling score was significantly higher in incident HAM/TSP as compared to healthy controls and tends to decline in HAM/TSP at 4-year follow-up (one sample t test). C IFN signaling was homogeneously down-regulated in all clinical groups by prednisolone treatment in vitro (left panel, Wilcoxon test p < 0.0001). Down-regulation was confirmed by decreased expression of the IFN-γ-regulated MHC Class II antigen presentation pathway (right panel, Wilcoxon test p < 0.001). D Ex vivo transcriptomic IFN signaling score measured by nCounter is significantly correlated with mRNA levels of previously identified HAM/TSP biomarkers CASP5, FCGR1A, STAT1, and CXCL10 (all p < 0.05 with Bonferroni correction), but not to HTLV-1 mRNAs Hbz and Tax. HC: healthy controls (open circles); AS asymptomatics (black circles), iHAM incident HAM/TSP (orange circles), HAM/TSP at 4-year follow-up (red circles), Con untreated in vitro PBMCs, Pred prednisolone-treated PBMCs in vitro. Paired samples from iHAM patients at diagnosis and at follow-up are identified by dashed lines.