Li Jie, Yin Chunyue, Okamoto Hiroaki, Jaffe Howard, Oldfield Edward H, Zhuang Zhengping, Vortmeyer Alexander O, Rushing Elisabeth J
Surgical Neurology Branch, National Institutes of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, Maryland, USA.
J Neuropathol Exp Neurol. 2006 Aug;65(8):826-33. doi: 10.1097/01.jnen.0000228204.19915.69.
Sporadic inclusion body myositis (IBM) is the most frequently acquired inflammatory myopathy of late adult life, yet its diagnostic criteria and pathogenesis remain poorly defined. Because effective treatment is lacking, research efforts have intensified to identify specific markers for this debilitating disorder. In this study, proteomic analysis of 4 cases of sporadic IBM was compared with 5 cases of inflammatory myopathy without clinicopathologic features of IBM to distinguish the IBM-specific proteome. Proteins were separated by 2-dimensional polyacrylamide gel electrophoresis and profiled by mass spectrometric sequencing. Expression of most proteins remained unchanged; however, 16 proteins were upregulated and 6 proteins were downregulated in IBM compared with cases of non-IBM inflammatory myopathy. These IBM-specific proteins included apolipoprotein A-I, amyloid beta precursor protein, and transthyretin, which have been associated with amyloidosis; superoxide dismutase, enolase, and various molecular chaperones indicate perturbations in detoxification, energy metabolism, and protein folding, respectively. The IBM-downregulated proteins mainly serve as carriers for muscle contraction and other normal muscle functions. We further applied Western blot and immunohistochemistry to verify the proteomic findings. This study validates proteomics as a powerful tool in the study of muscle disease and indicates a unique pattern of protein expression in IBM.
散发性包涵体肌炎（IBM）是成年晚期最常见的获得性炎性肌病，但其诊断标准和发病机制仍不明确。由于缺乏有效的治疗方法，研究工作已加强，以确定这种使人衰弱疾病的特异性标志物。在本研究中，对4例散发性IBM患者与5例无IBM临床病理特征的炎性肌病患者进行蛋白质组学分析，以区分IBM特异性蛋白质组。蛋白质通过二维聚丙烯酰胺凝胶电泳分离，并通过质谱测序进行分析。大多数蛋白质的表达保持不变；然而，与非IBM炎性肌病患者相比，IBM中有16种蛋白质上调，6种蛋白质下调。这些IBM特异性蛋白质包括与淀粉样变性相关的载脂蛋白A-I、淀粉样β前体蛋白和转甲状腺素蛋白；超氧化物歧化酶、烯醇化酶和各种分子伴侣分别表明解毒、能量代谢和蛋白质折叠存在紊乱。IBM中下调的蛋白质主要作为肌肉收缩和其他正常肌肉功能的载体。我们进一步应用蛋白质印迹法和免疫组织化学法来验证蛋白质组学研究结果。本研究证实蛋白质组学是研究肌肉疾病的有力工具，并表明IBM中存在独特的蛋白质表达模式。
