The Expanding Spectrum of Autoinflammatory Diseases

Autoinflammatory diseases are systemic disorders caused by genetic or acquired abnormalities in certain signaling pathways of the innate immune system. Dysregulated activation of the inflammasome, i.e. molecu-lar platforms responsible for the activation of caspase-1 and production of interleukin-1(3, causes autoinflam-mation. Familial Mediterranean fever (FMF), the most common genetic autoinflammatory disease, is charac-terized by a periodic fever and serositis. The complex and heterogeneous genetic background of Japanese FMF patients, accompanied by potential overlap with other rheumatic diseases, suggests crosstalk between genetic and environmental factors. Recently, FMF has been recognized as being part of a spectrum of autoin-flammatory syndromes named pyrin-associated autoinflammatory diseases. The discovery of a new mono-genic autoinflammatory disease, A20 haploinsufficiency, may provide novel insights into early-onset Behcet's-like diseases. In contrast, adult-onset Still's disease and Schnitzler's syndrome are acquired autoin-flammatory diseases without a monogenic abnormality. Although the concept of autoinflammatory diseases originally applied to monogenic hereditary recurrent fevers, it has been expanded to include non-genetic com-plex autoinflammatory diseases. Information concerning monogenic autoinflammatory diseases may prove useful for elucidating the molecular mechanisms underlying non-genetic autoinflammatory diseases.