Mutated NLRP3 assembles a hyperactive inflammasome, which causes excessive secretion of interleukin (IL)-1β and IL-18 and, ultimately, a spectrum of autoinflammatory disorders known as cryopyrinopathies of which neonatal-onset multisystem inflammatory disease (NOMID) is the most severe phenotype.
Unprovoked activation of innate immune pathways and increased secretion of interleukin (IL)-1β and IL-18 are responsible for the protean clinical manifestations and the marked inflammatory response that characterise most hereditary autoinflammatory disorders.
Muckle-Wells syndrome (MWS) is a rare autoinflammatory disorder associated with NLRP3 gene mutations, which cause excessive caspase-1 activation and processing of interleukin (IL)-1β and IL-18.