Feist E, Brehm A, Kallinich T, Krüger E
Klinik für Rheumatologie und Klinische Immunologie, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Deutschland.
Institut für Biochemie, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Deutschland.
Z Rheumatol. 2017 May;76(4):328-334. doi: 10.1007/s00393-017-0264-x.
Functional disorders of the proteasome can have a severe impact on the innate immune system. Characterized by an autosomal recessive mode of inheritance, this novel type of interferonopathy is considered to be a spectrum of diseases of proteasome-associated autoinflammatory syndromes (PRAAS). Accumulation of ubiquitinated proteins and the induction of type I interferon (IFN) genes seem to play a role in the pathogenesis. The typical clinical manifestations are lipodystrophy, skin, joint and muscle involvement accompanied by a remarkable variability of other associated symptoms. This article provides an overview on currently known molecular alterations as well as clinical similarities and differences of PRAAS. Furthermore, the reported effects of the immunosuppressive therapy approaches used so far are summarized.
蛋白酶体功能障碍可对先天性免疫系统产生严重影响。这种新型干扰素病以常染色体隐性遗传模式为特征,被认为是蛋白酶体相关自身炎症综合征(PRAAS)的一系列疾病。泛素化蛋白的积累和I型干扰素(IFN)基因的诱导似乎在发病机制中起作用。典型的临床表现为脂肪营养不良、皮肤、关节和肌肉受累,并伴有其他相关症状的显著变异性。本文概述了目前已知的PRAAS分子改变以及临床异同。此外,还总结了迄今为止所采用的免疫抑制治疗方法的报道效果。