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.
- Daniel L. Kastner
- John J. O'Shea
