A fever gene comes in from the cold

The pyrin domain was first noted in the familial Mediterranean fever protein from which it takes its name. It belongs to a structural superfamily that includes death domains, death effector domains and caspase activation and recruitment domains. Several genes underlying autoinflammatory diseases have at least one of these four death domain-fold motifs. Mutations in CIAS1, encoding cryopyrin, a leukocyte-specific member of this growing superfamily, have now been shown to cause both familial cold autoinflammatory syndrome and Muckle-Wells syndrome. These new findings add to the growing body of evidence that the dysregulation of leukocyte apoptosis may be a common molecular pathway leading to inflammatory disease.