Accumulation of autophagosome cargo protein p62 is common in idiopathic inflammatory myopathies.
Accumulation of autophagosome cargo protein p62 is common in idiopathic inflammatory myopathies.
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自噬体运蛋白p62的积聚在特发性炎症性肌病中很常见。
DOI：
10.55563/clinexprheumatol/6mp37n
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发表时间：
2021-03
影响因子：
3.7
通讯作者：
Corse, A. M.
中科院分区：
文献类型：
--
作者：
Milisenda, J. C.;Pinal-Fernandez, I;Lloyd, T. E.;Grau, J. M.;Miller, F. W.;Selva-O'Callaghan, A.;Christopher-Stine, L.;Stenzel, W.;Mammen, A. L.;Corse, A. M.
关键词：
肌纤维中p62聚集体的肌上皮下积聚被认为是散发性包涵体肌炎（sIBM）的特征。本研究的目的是分析p62免疫染色的模式和流行程度，并定量分析p62基因在大量不同类型的肌病和神经源性疾病患者的肌肉活检中的表达。对于p62免疫染色分析，纳入了2013年至2017年在约翰霍普金斯神经肌肉病理实验室进行p62免疫染色的所有肌肉活检患者（n=303）。比较组织学正常肌肉患者（29例）、炎症性肌病患者（136例）、非炎症性肌病患者（53例）和神经源性疾病患者（85例）p62免疫染色的患病率和模式。使用现有的RNAseq数据集分析p62的表达水平，该数据集包括皮肌炎（DM, n=39）、免疫介导的坏死性肌病（IMNM, n=49）、抗合成酶综合征（AS, n=18）和sIBM （n=23）患者以及20例组织学正常的肌肉活检。p62染色在正常活检中不存在，但在多发性肌炎（29%）、非炎症性肌病（均<31%）、神经源性疾病（31%）、皮肌炎（57%）、sIBM（92%）和IMNM（87%）的活检中存在。在所有研究的疾病中，p62积累在肌肉损伤更严重的活检中更为普遍。与其他组相比，sIBM活检的p62表达水平降低（校正0.04）。p62积累是对肌肉损伤的一般反应，而不是sIBM的特异性标志物。此外，在sIBM中，p62 RNA水平降低，这表明在这种疾病中，p62聚集不是由于过表达。
The subsarcolemmal accumulation of p62 aggregates in myofibres has been proposed to be characteristic of s poradic inclusion body myositis (sIBM). The objective of this study was to analyse the patterns and prevalence of p62 immunostaining and to quantitate p62 gene expression in muscle biopsies from a large number of patients with different types of myopathic and neurogenic disorders. For the p62 immunostaining analysis, all patients with a muscle biopsy immunostained for p62 at the Johns Hopkins Neuromuscular Pathology Laboratory from 2013 to 2017 were included (n=303). The prevalence and pattern of p62 immunostaining were compared between patients with histologically normal muscle (n=29), inflammatory myopathies (n=136), non-inflammatory myopathies (n=53), and neurogenic disorders (n=85). p62 expression levels were analysed using an existing RNAseq dataset including data from dermatomyositis (DM; n=39), immune-mediated necrotising myopathy (IMNM; n=49), antisynthetase syndrome (AS; n=18), and sIBM (n=23) patients as well as 20 histologically normal muscle biopsies. p62 staining was absent in normal biopsies, but present in biopsies from those with polymyositis (29%), non-inflammatory myopathies (all <31%), neurogenic disorders (31%), dermatomyositis (57%), sIBM (92%) and IMNM (87%). In all diseases studied, p62 accumulation was more prevalent in biopsies with more severe muscle damage. sIBM biopsies had decreased p62 expression levels compared to the other groups (corrected 0.04). p62 accumulation is a general response to muscle injury and not a specific marker for sIBM. Also, in sIBM, p62 RNA levels are decreased, suggesting that, in this disease, p62 aggregation is not due to overexpression.
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影响因子：
4.7
作者：
Lloyd TE;Christopher-Stine L;Pinal-Fernandez I;Tiniakou E;Petri M;Baer A;Danoff SK;Pak K;Casciola-Rosen LA;Mammen AL
通讯作者：
Mammen AL
影响因子：
2.8
作者：
Nakano, Satoshi;Oki, Mitsuaki;Kusaka, Hirofumi
通讯作者：
Kusaka, Hirofumi
影响因子：
27.4
作者：
Lilleker, James B.;Hodgson, Richard;Chinoy, Hector
通讯作者：
Chinoy, Hector
影响因子：
27.4
作者：
Pinal-Fernandez I;Casal-Dominguez M;Carrino JA;Lahouti AH;Basharat P;Albayda J;Paik JJ;Ahlawat S;Danoff SK;Lloyd TE;Mammen AL;Christopher-Stine L
通讯作者：
Christopher-Stine L
影响因子：
14.5
作者：
Benveniste, Olivier;Guiguet, Marguerite;Hilton-Jones, David
通讯作者：
Hilton-Jones, David