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Available from: Joost Frenkel, Dec 14, 2013
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    • "Thus the blockade of IL-1β may prove to be a fascinating adjunctive therapy for FMF. Indeed, in several case reports, colchicine-resistant FMF patients have shown immediate and sustained resolution of symptoms when treated with the IL-1 receptor antagonist, anakinra (Chae et al, 2006; Belkhir et al, 2007; Kuijk et al, 2007; Calligaris et al, 2008; Roldan et al, 2008). The dramatic therapeutic effect of anakinra is better known in another group of autoinflammatory diseases, the cryopyrin-associated periodic syndromes (Hawkins et al, 2003; Hoffman et al, 2004; Goldbach-Mansky et al, 2006). "
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    ABSTRACT: Familial Mediterranean fever (FMF) is a systemic autoinflammatory disorder characterized by seemingly unprovoked recurrent episodes of fever and serosal, synovial, or cutaneous inflammation. FMF is caused by recessively inherited mutations in MEFV, which encodes pyrin, and most of the mutations are present in the C-terminal end of the protein encoding B30.2 domain. The FMF carrier frequencies are extremely high in several eastern Mediterranean populations. Pyrin is expressed in granulocytes, monocytes, dendritic cells, and synovial fibroblasts. Pyrin regulates caspase-1 activation and consequently interleukin-1beta production through the interactions of its N-terminal PYRIN domain and C-terminal B30.2 domain with an adaptor protein, apoptosis-associated speck-like protein with a caspase-recruitment domain (ASC) and caspase-1 respectively. Pyrin is cleaved by caspase-1 and the cleaved N-terminal fragment translocates to nucleus and enhances ASC-independent nuclear factor (NF)-kappaB activation through interactions with p65 NF-kappaB and IkappaB-alpha. In addition to the regulatory role of pyrin for caspase-1, the cleavage of pyrin provides an important clue not only in understanding the molecular pathogenesis of FMF but also in developing new therapeutic targets for FMF.
    British Journal of Haematology 06/2009; 146(5):467-78. DOI:10.1111/j.1365-2141.2009.07733.x · 4.71 Impact Factor
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    Annals of the Rheumatic Diseases 12/2007; 66(11):1544-5. DOI:10.1136/ard.2007.070383 · 10.38 Impact Factor
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    ABSTRACT: Familial Mediterranean fever (FMF), a recessively inherited autoinflammatory disorder, is the prototype of a group of disorders termed systemic autoinflammatory diseases. Such diseases are characterized by seemingly unprovoked episodes of inflammation without evidence of high-titer autoantibodies or antigen-specific T cell. Repeated bouts of inflammation may lead to systemic AA protein deposition, making FMF a potentially fatal disease. Pyrin, the protein mutated in FMF, regulates caspase-1 activation and consequently IL-1beta production. Although colchicine is the standard prophylactic therapy for attacks and amyloid deposition, some patients fail to respond or cannot tolerate its side effects. Anticytokine therapies have shown promise in the treatment of autoinflammatory disorders in children. We report on the use of the recombinant interleukin 1 receptor antagonist anakinra in one child with therapy-resistant FMF. The patient experienced immediate, sustained resolution of symptoms and laboratory markers of inflammation, and also, possibly, a reduced long-term risk of AA amyloidosis.
    Joint, bone, spine: revue du rhumatisme 08/2008; 75(4):504-5. DOI:10.1016/j.jbspin.2008.04.001 · 2.90 Impact Factor
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