Extended Data Fig. 3 |. Cytokine and mRNA changes associated with iRHOM2 deficiency.

(a) Heat map of multiplex measurements of 48 cytokine levels in HC plasma using the Luminex system. (b) Volcano plot of whole blood RNA-seq showing upregulated genes (red) and down regulated genes (blue) in the patient sample from iRHOM2 deficient patients compared to HC. (c) GSEA based on the patient whole blood RNA-seq data in comparison to healthy control. NES; normalized enrichment score. (d) Table of ADAM17 regulated molecules extracted from whole blood RNA-seq. (e) Volcano plot of gene expression with fold difference between log₂ normalized expression shown in Fig. 5d versus −log₁₀ adjusted P-value in whole blood. Vertical grey lines indicate fold changes, with a cut off ±2. The horizontal line represents a p-value of 1⁻¹⁰. (f) Similar with Fig. 5f, volcano plot of gene expression before and after 3 hours stimulation in T cells from 4 HC (left panel) and 4 patients (right panel). Red dots represent upregulated mRNAs and blue dots indicate downregulated mRNAs. (g) Hierarchical clustering of stimulated T cells RNA-seq data in the different time points using HC samples. Time is shown on the x-axis and gene expression levels are shown on the y-axis. Mean expression was used from 4 HC samples. Statistical significance was calculated by using the Wald test for hypothesis testing (b, e, f).