Cryopyrin-associated periodic syndromes: background and therapeutics.
Cryopyrin-associated periodic syndromes (CAPS) are caused by mutations of the gene encoding the NLR family protein NLRP3, which together with caspase-1 and adaptor proteins constitutes a protein complex termed the inflammasome. In innate immune reactions, a variety of stimuli activate the NLRP3 inflammasome, triggering caspase-1 to process proIL-1 and thus to produce mature IL-1. Excessive production of IL-1 by monocytes/macrophages is the central pathophysiology of CAPS, and daily injection of the IL-1 receptor antagonist anakinra rapidly ameliorates the inflammatory symptoms in most cases. Furthermore, double-blind, placebo-controlled clinical trials have recently confirmed the efficacy and safety of rilonacept, a fusion protein of the IL-1 receptor and IgG Fc, and canakinumab, a human anti-IL-1 monoclonal antibody, as novel long-lasting agents for treating CAPS.
Graduate School of Health Care Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan. tetsuo.kubota.mtec@tmd.ac.jp
Tetsuo
T
Kubota
Ryuji
R
Koike
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D002352:Carrier Proteins / Q000235:genetics* / Q000276:immunology; D056587:Cryopyrin-Associated Periodic Syndromes / Q000235:genetics* / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D002352:Carrier Proteins; D007375:Interleukin-1; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D011993:Recombinant Fusion Proteins; C541220:canakinumab; C531377:rilonacept