PW03-027 - CASP1 Variants and Live Cell Imaging

Patients with unexplained recurrent febrile episodes and CASP1 variants suffer from systemic sterile inflammation despite reduced secretion of IL-1s. As previously demonstrated by our group CASP1 variants lead to reduced enzymatic activity of procaspase-1 by destabilizing the tertiary structure of the caspase-1 tetramer. A possible explanation for an alternative pro-inflammatory pathway has been provided by Lamkanfi and colleagues indicating an association between enzymatically inactive procaspase-1 and receptor interacting protein kinase 2 (RIP2) leading to NF-kB activation.