Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Center for Educational Research and Development, Wakayama Medical University, Wakayama, Japan.
Neuropathol Appl Neurobiol. 2020 Oct;46(6):579-587. doi: 10.1111/nan.12614. Epub 2020 Mar 25.
Nakajo-Nishimura syndrome (NNS) is an autosomal recessive disease caused by biallelic mutations in the PSMB8 gene that encodes the immunoproteasome subunit β5i. There have been only a limited number of reports on the clinicopathological features of the disease in genetically confirmed cases.
We studied clinical and pathological features of three NNS patients who all carry the homozygous p.G201V mutations in PSMB8. Patients' muscle specimens were analysed with histology and immunohistochemistry.
All patients had episodes of typical periodic fever and skin rash, and later developed progressive muscle weakness and atrophy, similar to previous reports. Oral corticosteroid was used for treatment but showed no obvious efficacy. On muscle pathology, lymphocytes were present in the endomysium surrounding non-necrotic fibres, as well as in the perimysium perivascular area. Nearly all fibres strongly expressed MHC-I in the sarcolemma. In the eldest patient, there were abnormal protein aggregates in the sarcoplasm, immunoreactive to p62, TDP-43 and ubiquitin antibodies.
These results suggest that inflammation, inclusion pathology and aggregation of abnormal proteins underlie the progressive clinical course of the NNS pathomechanism.
Nakajo-Nishimura 综合征（NNS）是一种常染色体隐性疾病，由 PSMB8 基因的双等位基因突变引起，该基因编码免疫蛋白酶体亚基β5i。在基因确诊病例中，该疾病的临床病理特征仅有少数报道。
我们研究了 3 名 NNS 患者的临床和病理特征，他们均携带 PSMB8 中的纯合 p.G201V 突变。对患者的肌肉标本进行组织学和免疫组织化学分析。
所有患者均有典型的周期性发热和皮疹发作，随后出现进行性肌肉无力和萎缩，与以往报道相似。曾使用口服皮质类固醇治疗，但无明显疗效。肌肉病理学检查显示，在非坏死纤维周围的肌内膜和血管周围的肌周膜中存在淋巴细胞。几乎所有纤维的肌膜上均强烈表达 MHC-I。在最年长的患者中，肌浆中存在 p62、TDP-43 和泛素抗体免疫反应性的异常蛋白聚集体。
这些结果表明，炎症、包涵体病理学和异常蛋白的聚集是 NNS 发病机制进行性临床病程的基础。
