Activation of the pyrin inflammasome through the RoA signalling pathway uncovers an interesting molecular connection between hyperimmunoglobulinemia D syndrome and familial Mediterranean fever.
Mutations in the genes encoding pyrin and mevalonate kinase (MVK) cause distinct interleukin-1β (IL-1β)-mediated autoinflammatory diseases: familial Mediterranean fever (FMF) and hyperimmunoglobulinemia D syndrome (HIDS).
These included the TNFRSF1A locus (formerly known as TNFRI), which is involved in autosomal dominant tumor necrosis factor receptor-associated periodic syndrome on chromosome 12p13, the familial Mediterranean fever locus (MEFV) on chromosome 16p13, the hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) locus on chromosome 12q24, and the Muckle-Wells syndrome/familial cold urticaria (MWS/FCU) locus on distal chromosome 1q44.