Department of Pathology, University of California San Francisco, San Francisco, CA 94143, USA.
Acta Neuropathol Commun. 2013 Jul 1;1:29. doi: 10.1186/2051-5960-1-29.
Inclusion body myositis (IBM) is a slowly progressive inflammatory myopathy of the elderly that does not show significant clinical improvement in response to steroid therapy. Distinguishing IBM from polymyositis (PM) is clinically important since PM is steroid-responsive; however, the two conditions can show substantial histologic overlap.
We performed quantitative immunohistochemistry for (1) autophagic markers LC3 and p62 and (2) protein aggregation marker TDP-43 in 53 subjects with pathologically diagnosed PM, IBM, and two intermediate T cell-mediated inflammatory myopathies (polymyositis with COX-negative fibers and possible IBM). The percentage of stained fibers was significantly higher in IBM than PM for all three immunostains, but the markers varied in sensitivity and specificity. In particular, both LC3 and p62 were sensitive markers of IBM, but the tradeoff between sensitivity and specificity was smaller (and diagnostic utility thus greater) for LC3 than for p62. In contrast, TDP-43 immunopositivity was highly specific for IBM, but the sensitivity of this test was low, with definitive staining present in just 67% of IBM cases.
To differentiate IBM from PM, we thus recommend using a panel of LC3 and TDP-43 antibodies: the finding of <14% LC3-positive fibers helps exclude IBM, while >7% of TDP-43-positive fibers strongly supports a diagnosis of IBM. These data provide support for the hypothesis that disruption of autophagy and protein aggregation contribute to IBM pathogenesis.
包涵体肌炎（IBM）是一种老年人中进展缓慢的炎症性肌病，对类固醇治疗没有明显的临床改善。将 IBM 与多发性肌炎（PM）区分开来在临床上很重要，因为 PM 对类固醇有反应；然而，这两种情况在组织学上可能有很大的重叠。
我们对 53 例经病理诊断为 PM、IBM 和两种中间 T 细胞介导的炎症性肌病（cox 阴性纤维的多发性肌炎和可能的 IBM）的患者进行了（1）自噬标记物 LC3 和 p62 和（2）蛋白聚集标记物 TDP-43 的定量免疫组化染色。与 PM 相比，IBM 中染色纤维的百分比在所有三种免疫染色中均显著升高，但标记物的敏感性和特异性不同。特别是，LC3 和 p62 都是 IBM 的敏感标志物，但 LC3 的敏感性和特异性之间的权衡（因此诊断效用更大）小于 p62。相比之下，TDP-43 免疫阳性对 IBM 具有高度特异性，但该检测的敏感性较低，只有 67%的 IBM 病例存在明确染色。
为了将 IBM 与 PM 区分开来，我们建议使用 LC3 和 TDP-43 抗体的组合：<14%的 LC3 阳性纤维有助于排除 IBM，而>7%的 TDP-43 阳性纤维强烈支持 IBM 的诊断。这些数据支持自噬和蛋白聚集破坏导致 IBM 发病机制的假说。
