Fig. 1

Pyrin inflammasome activation in FMF. MEFV gene, located on the short arm of chromosome 16 (16p 13.3), is made of 10 exons and encodes the pyrin protein. Pyrin is composed of the five domains PYD, bZIP transcription factor, B-box, α-helical coiled-coil, and B30.2 domains. The C-terminal domain, B30.2, is the most important domain where the most common FMF mutations (M680I, M694I, M694V, V726A) are clustered. MEFV mutations activate pyrin which form with pro-caspase-1 and ASC a multiprotein complex called inflammasome. The assembly of the pyrin inflammasome initiates autocatalytic activation of caspase-1 which in turn cleaves and converts pro-IL-1β to active IL-1β leading to inflammation and contributing to FMF clinical manifestations (fever, serositis, joint pain …). MEFV: MEditerranean FeVer; ASC: Apoptosis-associated speck-like protein, bZIP: Basic leucine zipper; CARD: Caspase recruitment domain; IL-1β: Interleukin-1 beta; PYD: Pyrin domain