In pro-apoptotic signaling pathways, the interaction between the different initiator units such as the death receptor Fas, the various adaptor proteins and caspases is primarily mediated by three structurally related protein–protein domains called death domain (DD), death effector domain (DED), and caspase-recruitment domain (CARD) [1,2]. While analyzing the sequence of the recently identified ...

Background FMF is a systemic auto-inflammatory disorder, characterized by recurrent episodes of fever and serosal inflammation. The MEF gene, which is associated with FMF, encodes for the protein pyrin. FMF associated mutations, interrupt with pyrin normal function, leading to activation of the innate immune system and overexpression of IL-1b, and consequently to a systemic inflammatory respons...

Familial Mediterranean fever is an autosomal recessive autoinflammatory disorder mainly affecting Mediterranean populations, which is associated with mutations of the MEFV gene that encodes pyrin. Functional studies suggest that pyrin is implicated in the maturation and secretion of interleukin-1 (IL-1). The IL-1 receptor antagonist or anti-IL-1 monoclonal antibody may therefore represent a rat...

Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC)/target of methylation-induced silencing/PYCARD represents one of only two proteins encoded in the human genome that contains a caspase recruitment domain (CARD) together with a pyrin, AIM, ASC, and death domain-like (PAAD)/PYRIN/DAPIN domain. CARDs regulate caspase family proteases. We show here that ASC binds...

Background The p.E148Q variant in pyrin is present different populations at a frequency up to 29%[1], and has been associated with inflammatory diseases including vasculitis familial Mediterranean fever (FMF)[2,3]. pathogenicity of FMF unclear, highly debated the literature especially when observed cis or trans single, typically recessive, mutation. If it could modify expressivity pathogenic al...

background: systemic-onset juvenile idiopathic arthritis (sojia) is an autoinflammatory disease with complex genetic trait starts in children less than 16 years of age with fever and cutaneous rash. despite, the main genetic factors that may play a role in sojia have not yet been identified. high level of interleukin-1beta in the blood of sojia patients has been reported. the production and sec...