Neven Bénédicte, Prieur Anne-Marie, Quartier dit Maire Pierre
Hôpital Necker-Enfants-Malades, Paris, France.
Nat Clin Pract Rheumatol. 2008 Sep;4(9):481-9. doi: 10.1038/ncprheum0874. Epub 2008 Jul 29.
Cryopyrinopathies are a group of rare autoinflammatory diseases that includes familial cold autoinflammatory syndrome, Muckle-Wells syndrome and chronic infantile neurologic cutaneous articular syndrome (also termed neonatal-onset multisystemic inflammatory disease). These syndromes were initially considered to be distinct disease entities despite some clinical similarities; however, mutations of the same gene have since been found in all three cryopyrinopathies. These diseases, therefore, are not separate but represent a continuum of subphenotypes. The gene in question, CIAS1 (now renamed NLRP3) encodes NALP3 (also known as cryopyrin). NALP3 is an important mediator of inflammation and interleukin 1beta processing. New therapies based on biologic agents that specifically target interleukin 1beta are currently being developed. These new agents have provided very encouraging results for patients with these long-lasting inflammatory conditions--which used to be considered refractory to treatment. The development of therapeutic options for these cryopyrinopathies illustrates effective translation of basic science to clinical practice and the convergence of human genetics and targeted therapies.
冷吡啉相关周期性综合征是一组罕见的自身炎症性疾病，包括家族性寒冷性自身炎症综合征、穆克-韦尔斯综合征和慢性婴儿神经皮肤关节综合征（也称为新生儿期起病的多系统炎症性疾病）。尽管这些综合征在临床上有一些相似之处，但最初被认为是不同的疾病实体；然而，后来在所有这三种冷吡啉相关周期性综合征中都发现了相同基因的突变。因此，这些疾病并非相互独立，而是代表了一系列亚表型。所讨论的基因CIAS1（现重新命名为NLRP3）编码NALP3（也称为冷吡啉）。NALP3是炎症和白细胞介素1β加工的重要介质。目前正在研发基于特异性靶向白细胞介素1β的生物制剂的新疗法。这些新制剂为患有这些长期炎症性疾病的患者带来了非常令人鼓舞的结果，而这些疾病过去曾被认为难以治疗。这些冷吡啉相关周期性综合征治疗方案的发展体现了基础科学向临床实践的有效转化以及人类遗传学与靶向治疗的融合。
