Gene expression signatures validate plasma classifier and point to distinctive T-cell and IFN-γ–driven etiology of HLH. (A) Gene set enrichment plot showing the enrichment score of the ranked gene list in the IFN–γ response signature of CD8⁺ T cells and CD68⁺ monocytes from subjects with HLH and severe sepsis. (B) Genes included in the leading edge analysis of the IFN-γ response signature (A) are presented graphically. The leading edge consists of the subset of genes in the signature where the running sum of the enrichment score reaches its maximum deviation from zero in panel A. The color describes whether the gene is (yellow) or is not (blue) present in leading-edge genes in the CD8 or CD68 datasets. (C) Relative gene expression of the leading edge genes that are significantly enriched in the INF-γ response signature from the CD8 and CD68 subpopulations are presented in a heatmap, with each column representing cell-specific transcriptome from a single subject.