Abstract Down syndrome (DS), affecting 1 in 700 live births, is the most prevalent chromosomal disorder among newborns. Recognizable by classical clinical features, patients with DS are susceptible to various immunological misbalances. Inflammasome is (mis)activated in several immune-mediated diseases, however studies on individuals with DS are lacking. The present study evaluated the gene expression of NLRP1, NLRP3 and IL-1β in individuals with DS, aiming to understand their susceptibility to immune-mediated diseases. In addition, we assessed whether the individuals with DS present a differential inflammatory response after in vitro infection using PBMCs. For the gene expression assay, 20 individuals with DS and 15 healthy individuals for the control group (CT) were included, while the in vitro infection assay included 10 subjects. mRNA levels from individuals with DS group showed 1.9-fold change (FC) downregulation for NLRP1 (p=0.0001), but no differences for NLRP3 and IL1β. We did not observe significant differences between lipopolysaccharide (LPS)-treated and untreated cells in our in vitro assays. The differential expression of NLRP1 in individuals with DS suggests a potential association with susceptibility to the development of immune-mediated diseases, but further analysis is needed to confirm this relationship. , (DS) 70 births newborns features misbalances misactivated mis activated immunemediated immune mediated diseases lacking NLRP IL1β ILβ IL 1β β addition PBMCs 2 CT (CT subjects 1.9fold 19fold fold 1.9 9 FC (FC p=0.0001, p00001 p p=0.0001 0 0001 (p=0.0001) LPStreated LPS treated assays relationship (DS 7 9fold 19 1. p0000 p=0.000 000 (p=0.0001 p000 p=0.00 00 (p=0.000 p00 p=0.0 (p=0.00 p0 p=0. (p=0.0 p=0 (p=0. p= (p=0 (p= (p