[Biological and clinical aspects of Muckle-Wells syndrome]

Muckle-Wells syndrome (MWS), as well as familial cold autoinflammatory syndrome (FCAS) and chronic infantile neurological cutaneous and articular syndrome (CINCA), arises from a missense mutation in the CIAS1 gene. Current progress of biology revealed that NALP3, a protein coded by the CIAS1 and expressed in monocytes, recognizes some bacterial products or harmful metabolites invaded in the cytoplasm, and forms inflammasome with other molecules. As a result, caspase-1 is activated leading to cleavage of pro-IL-1beta and extracellular release of IL-1beta. NALP3 of patients with MWS can be spontaneously activated without obvious stimulation, which causes recurrent attacks of inflammatory symptoms characterized by fever, urticarial rash, conjunctivitis and arthritis, and some patients develop amyloidosis. In addition, sensorineural hearing disturbance progresses gradually. Recently, significant efficacy of anakinra, a recombinant IL-1 receptor antagonist, has been demonstrated in treatment of MWS. So far, only a few cases have been reported from Japan, however an accurate diagnosis has to be established for the latent cases who have not received optimum treatment before occurrence of irreversible deafness or renal failure.