Activation of the pyrin inflammasome through the RhoA signaling pathway in FMF and HIDS

Mutations in the genes encoding pyrin and mevalonate kinase (MVK) cause the autoinflammatory diseases familial Mediterranean fever (FMF) and hyperimmunoglobulinemia D syndrome (HIDS), respectively. The inflammation of both diseases is mediated by interleukin-1β (IL-1β). Recently it has been reported that pyrin forms an inflammasome, a multiprotein complex that mediates the maturation of IL-1β by activating caspase-1, in response to bacterial modifications of RhoA. However, the precise molecular mechanism by which the pyrin inflammasome is activated is unknown.