IL-1 blockade in autoinflammatory syndromes.
IL-1 blockade in autoinflammatory syndromes.
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DOI：
10.1146/annurev-med-061512-150641
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发表时间：
2014
影响因子：
10.5
通讯作者：
Goldbach-Mansky R
中科院分区：
文献类型：
--
作者：
Jesus AA;Goldbach-Mansky R
单基因自身炎性综合征表现为过度的全身性炎症，包括发热、皮疹、关节炎和器官特异性炎症，并且是由编码调节先天性炎症途径的蛋白质的单基因缺陷引起的。两种白细胞介素-1（IL-1）调节基因NLRP 3和IL 1 RN的致病性变体导致两种严重的和早发性自身炎症综合征，CAPS（cryopyrin相关周期性综合征）和DIRA（IL-1受体拮抗剂缺乏）。导致CAPS和DIRA的突变的发现导致了临床和基础研究，揭示了IL-1在广泛的免疫失调状况中的关键作用。NLRP 3编码cryopyrin，一种细胞内“分子传感器”，形成多分子平台，NLRP 3炎性体，其将“危险识别”与促炎细胞因子IL-1β的激活联系起来。靶向IL-1的药物在治疗CAPS和DIRA中的成功和安全性特征鼓励了它们在包括经典遗传性周期性发热综合征在内的其他自身炎症综合征中的广泛应用（家族性地中海热、TNF受体相关的周期性综合征和高免疫球蛋白血症D伴周期性发热综合征）和其他遗传上不明确的免疫失调病症，包括Still's、Behcet's、和Schnitzler病。代谢底物（如尿酸盐、神经酰胺、胆固醇和葡萄糖）的积累可以触发NLRP 3炎性体的事实将代谢应激与IL-1β介导的炎症联系起来，并为在流行疾病（如痛风、糖尿病和冠状动脉疾病）中治疗靶向IL-1提供了基本原理。
Monogenic autoinflammatory syndromes present with excessive systemic inflammation including fever, rashes, arthritis, and organ-specific inflammation and are caused by defects in single genes encoding proteins that regulate innate inflammatory pathways. Pathogenic variants in two interleukin-1 (IL-1)–regulating genes, NLRP3 and IL1RN, cause two severe and early-onset autoinflammatory syndromes, CAPS (cryopyrin associated periodic syndromes) and DIRA (deficiency of IL-1 receptor antagonist). The discovery of the mutations that cause CAPS and DIRA led to clinical and basic research that uncovered the key role of IL-1 in an extended spectrum of immune dysregulatory conditions. NLRP3 encodes cryopyrin, an intracellular “molecular sensor” that forms a multimolecular platform, the NLRP3 inflammasome, which links “danger recognition” to the activation of the proinflammatory cytokine IL-1β. The success and safety profile of drugs targeting IL-1 in the treatment of CAPS and DIRA have encouraged their wider use in other autoinflammatory syndromes including the classic hereditary periodic fever syndromes (familial Mediterranean fever, TNF receptor–associated periodic syndrome, and hyperimmunoglobulinemia D with periodic fever syndrome) and additional immune dysregulatory conditions that are not genetically well defined, including Still’s, Behcet’s, and Schnitzler diseases. The fact that the accumulation of metabolic substrates such as monosodium urate, ceramide, cholesterol, and glucose can trigger the NLRP3 inflammasome connects metabolic stress to IL-1β-mediated inflammation and provides a rationale for therapeutically targeting IL-1 in prevalent diseases such as gout, diabetes mellitus, and coronary artery disease.
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影响因子：
27.4
作者：
Bodar, E. J.;Kuijk, L. M.;Frenkel, J.
通讯作者：
Frenkel, J.
DOI：
10.1056/nejmoa0807865
发表时间：
2009-06-04
期刊：
The New England journal of medicine
影响因子：
--
作者：
Aksentijevich I;Masters SL;Ferguson PJ;Dancey P;Frenkel J;van Royen-Kerkhoff A;Laxer R;Tedgård U;Cowen EW;Pham TH;Booty M;Estes JD;Sandler NG;Plass N;Stone DL;Turner ML;Hill S;Butman JA;Schneider R;Babyn P;El-Shanti HI;Pope E;Barron K;Bing X;Laurence A;Lee CC;Chapelle D;Clarke GI;Ohson K;Nicholson M;Gadina M;Yang B;Korman BD;Gregersen PK;van Hagen PM;Hak AE;Huizing M;Rahman P;Douek DC;Remmers EF;Kastner DL;Goldbach-Mansky R
通讯作者：
Goldbach-Mansky R
DOI：
10.1084/jem.20102049
发表时间：
2011-03-14
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bulua AC;Simon A;Maddipati R;Pelletier M;Park H;Kim KY;Sack MN;Kastner DL;Siegel RM
通讯作者：
Siegel RM
影响因子：
11.1
作者：
Bauernfeind, Franz;Hornung, Veit
通讯作者：
Hornung, Veit
Anakinra在青少年中具有抗秋水仙碱的家族地中海热的功效。
影响因子：
3.6
作者：
Calligaris, Lorenzo;Marchetti, Federico;Tommasini, Alberto;Ventura, Alessandro
通讯作者：
Ventura, Alessandro