Immunological and transcriptional characterization of PBMCs response to NLRP1 pathway stimulation in MS patients carrying putatively pathogenic variants in NLRP1 gene in comparison to healthy controls. (A) depicts results of RNAseq transcriptional profiling for a selection of genes belonging to broad inflammasome pathway as defined by KEGG NOD-like receptor pathway. A tendency towards upregulation of genes in the pathway is present and the recapitulated with GSEA pathway analysis, presented in (B) showing a tendency of the pathway towards upregulation. (C) depicts characterization of IL-1β as the main effector of NLRP1 pathway activation. We were able to both validate the increased expression of IL1B detected in RNAseq and to demonstrate increased production of IL-1β. The specificity of findings for IL-1β was demonstrated by measuring TNF-α production in the same cell culture supernatants (data not shown)8. There was no significant difference in the TNF-α secretion between PBMCs of MS patients with mutations in NLRP1 gene and healthy subjects. The * and ** annotations in (C) denote significance attained at threshold P = 0.05 and P = 0.01, respectively. The intervals correspond to standard error measure (SEM) of the measurements.