Department of Paediatrics, University of Genoa, Pediatria II, Reumatologia, IRCCS G. Gaslini, Genoa, Italy.
Autoimmun Rev. 2012 Nov;12(1):81-6. doi: 10.1016/j.autrev.2012.07.027. Epub 2012 Aug 2.
Inherited autoinflammatory syndromes are conditions caused by mutations of proteins playing a pivotal role in the regulation of the innate immunity leading to an uncontrolled inflammation. The understanding of the molecular pathways involved in these disorders has shed a new light on the pattern of activation and maintenance of the inflammatory response and disclosed new molecular therapeutic targets. In this review we give a start of the art of the use of biologics in these disorders.
The dramatic response to anti IL-1 drugs in cryopyrin-associated periodic syndromes represents the brightest example of the possibility to completely dampen inflammation in these severe disorders with the selective blockade of a single pivotal cytokine. Periodic fevers are characterized by recurrent episodes of fever, usually treated with on demand steroids. However the increasing frequency of fever episodes or the development of a chronic disease course may require a continuous long-term treatment, with anti-TNF or IL-1 blockers in mevalonate kinase deficiency and TNF-receptor associated periodic syndrome. Anti-IL-1 treatment is also effective in FMF patients resistant or partially responsive to colchicine. The deficiency of the interleukin-1-receptor antagonist (DIRA) is caused by mutations in the gene encoding for the interleukin-1 receptor antagonist (IL-1Ra). In this case t he recombinant IL-1Ra (anakinra) is the treatment of choice. Due to their extreme rarity the response to the available biologic drugs in other autoinflammatory diseases is still largely anecdotal.
遗传性自身炎症性疾病是由在固有免疫调节中起关键作用的蛋白突变引起的疾病，导致炎症失控。对这些疾病相关分子途径的理解为炎症反应的激活和维持模式提供了新的认识，并揭示了新的分子治疗靶点。在这篇综述中，我们介绍了生物制剂在这些疾病中的应用现状。
在 Cryopyrin 相关周期性综合征中，抗 IL-1 药物的显著疗效代表了一种可能，即在这些严重疾病中，通过选择性阻断单一关键细胞因子，完全抑制炎症。周期性发热的特征是反复出现发热，通常按需用类固醇治疗。然而，发热发作的频率增加或发展为慢性疾病过程可能需要长期持续治疗，即对甲羟戊酸激酶缺乏症和 TNF 受体相关周期性综合征使用抗 TNF 或 IL-1 阻滞剂。抗 IL-1 治疗对不耐受或部分对秋水仙碱有反应的 FMF 患者也有效。白细胞介素-1 受体拮抗剂（DIRA）缺乏症是由编码白细胞介素-1 受体拮抗剂（IL-1Ra）的基因突变引起的。在这种情况下，重组 IL-1Ra（anakinra）是首选治疗方法。由于这些疾病极为罕见，因此在其他自身炎症性疾病中，对现有生物药物的反应在很大程度上仍属于传闻。
