Mendell J R, Sahenk Z, Gales T, Paul L
Department of Neurology, College of Medicine, Ohio State University, Columbus 43210.
Arch Neurol. 1991 Dec;48(12):1229-34. doi: 10.1001/archneur.1991.00530240033013.
Inclusion body myositis (IBM) represents a serious debilitating disease of muscle without identifiable cause or treatment. Muscle biopsy specimens have characteristic rimmed vacuoles, varying degrees of inflammation, and, most importantly, cytoplasmic and intranuclear filamentous inclusions of unknown composition. Fresh-frozen sections of muscle biopsy specimens from 24 IBM cases were stained with Congo red dye (pH, 10.5 to 11.0). Control biopsy specimens included polymyositis, dermatomyositis, hereditary vacuolar myopathies of unknown cause, acid maltase deficiency, distal myopathy, oculopharyngeal dystrophy, and chloroquine myopathy. Sections were also immunostained with antibody to transthyretin, human P component, and immunoglobulin light chains. In the vacuolated fibers in IBM, amyloidogenic green-birefringent deposits were seen. Some deposits were delicate and wispy appearing, and others were plaque-like. The size of deposits varied, measuring 1 x 2 to 8 microns, and rarely up to 20 microns in length. The number of amyloid-positive fibers correlated with the number of vacuolated fibers. Similar deposits were seen in one case of distal myopathy and one hereditary vacuolar myopathy. Other control cases were negative for amyloid deposits. Antibody staining for known amyloidogenic proteins was negative. This study demonstrates that the filaments in IBM share properties with amyloid proteins. The location implies that this amyloid material is formed intracellularly, rather than having a systemic derivation. The association of amyloid deposits with autophagic vacuoles in IBM raises the likely possibility that the filaments represent a modification of a normal protein within an acidic degradative vacuolar compartment. An alternative possibility, considering the shared properties of IBM filaments and prions (which include size and amyloidogenic properties), is that IBM represents a human prion disease.(ABSTRACT TRUNCATED AT 250 WORDS)
包涵体肌炎（IBM）是一种严重的、导致肌肉衰弱的疾病，病因不明且尚无有效治疗方法。肌肉活检标本具有特征性的镶边空泡、不同程度的炎症，最重要的是，含有成分不明的胞质和核内丝状包涵体。对24例IBM患者的肌肉活检标本新鲜冰冻切片进行刚果红染色（pH值为10.5至11.0）。对照活检标本包括多肌炎、皮肌炎、病因不明的遗传性空泡性肌病、酸性麦芽糖酶缺乏症、远端肌病、眼咽型肌营养不良症和氯喹肌病。切片还用抗转甲状腺素蛋白、人P成分和免疫球蛋白轻链抗体进行免疫染色。在IBM的空泡化纤维中，可见淀粉样变的绿色双折射沉积物。一些沉积物纤细呈细丝状，另一些则呈斑块状。沉积物大小不一，长1×2至8微米，很少长达20微米。淀粉样阳性纤维的数量与空泡化纤维的数量相关。在1例远端肌病和1例遗传性空泡性肌病中也发现了类似沉积物。其他对照病例的淀粉样沉积物呈阴性。已知淀粉样变蛋白的抗体染色为阴性。本研究表明，IBM中的细丝与淀粉样蛋白具有共同特性。其位置表明这种淀粉样物质是在细胞内形成的，而非源自全身。IBM中淀粉样沉积物与自噬空泡的关联增加了细丝代表酸性降解性空泡隔室内正常蛋白质修饰的可能性。考虑到IBM细丝与朊病毒的共同特性（包括大小和淀粉样变特性），另一种可能性是IBM代表一种人类朊病毒疾病。（摘要截稿于250字）
