蛋白酶体相关自身炎症综合征研究进展

Research advances in proteasome-associated autoinflammatory syndrome

随着对自身炎症性疾病研究的不断深入,近年来发现了由蛋白酶体基因突变所致的一系列临床综合征,包括中条-西村综合征、伴脂肪代谢障碍的日本炎症综合征、关节挛缩-肌萎缩-小细胞贫血-脂膜炎相关脂营养不良综合征以及慢性非典型中性粒细胞性皮炎伴脂营养不良和发热。这类疾病统称为蛋白酶体相关自身炎症综合征或蛋白酶体病。与目前已知的由白细胞介素(IL)-1介导的自身炎症性疾病相比,蛋白酶体相关自身炎症综合征的基因突变导致蛋白酶体功能障碍、Ⅰ型干扰素(IFN)持续产生,且对IL-1抑制剂的治疗无反应。针对IFN途径的JAK1/JAK2抑制剂可望为这类患者带来疗效。

With the insights into autoinflammatory diseases, the mutations in proteasome cause a syndrome that has previ- ously been referred to as Nakajo-Nishimura syndrome （NNS）, Japanese autoinflammatory syndrome with lipodystrophy （JASL）, joint contractures, muscle atrophy, microcytic anemia, and pan- niculitis-induced childhood- onset lipodystrophy （JMP） syn- drome, or chronic atypical neutrophilic dermatosis with lipo- dystrophy and elevated temperature （CANDLE）. These dis- ease spectrum is referred to as proteasome-associated autoin- flammatory syndrome （PRAAS）. In contrast to what occurs in many currently known interleukin-1 mediated autoinflammato- ry diseases, mutations in proteasome lead to proteasome dys- function and chronic type I IFN production, and which have no response to IL-1 inhibition treatment. The JAK1/JAK2 in- hibitor which blocks IFN signaling may be effective in patients with PRAAS.