Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Department of Neurology, Tenri Hospital, Tenri, Japan.
Mov Disord. 2019 Oct;34(10):1452-1463. doi: 10.1002/mds.27794. Epub 2019 Jul 19.
Previous studies that have investigated the potential of in vivo abnormal α-synuclein deposits as a pathological biomarker for PD included few participants and reported different diagnostic accuracies. Here, we aimed to confirm the diagnostic value of in vivo α-synuclein deposits in PD through a systematic review and meta-analysis, with special emphasis on determining the tissue most suitable for examination and assessing whether anti-native α-synuclein or anti-phosphorylated α-synuclein antibodies should be used. Databases were searched on December 30, 2018. We finally included 41 case-control studies that examined in vivo tissue samples using anti-native α-synuclein or anti-phosphorylated α-synuclein antibody in PD patients and controls. Using a univariate random-effects model, pooled sensitivity and specificity (95% confidence interval) of anti-native α-synuclein antibody were 0.54 (0.49-0.60) and 0.72 (0.68-0.76) for the gastrointestinal tract and 0.76 (0.60-0.89) and 0.60 (0.43-0.74) for the skin. Pooled sensitivity and specificity (95% confidence interval) of anti-phosphorylated α-synuclein antibody were 0.43 (0.37-0.48) and 0.82 (0.78-0.86) for the gastrointestinal tract, 0.76 (0.69-0.82) and 1.00 (0.98-1.00) for the skin, 0.42 (0.26-0.59) and 0.94 (0.84-0.99) for the minor salivary glands, and 0.66 (0.51-0.79) and 0.96 (0.86-1.00) for the submandibular glands. Although ubiquitous heterogeneity between the included studies should be noted when interpreting our results, our analyses demonstrated the following: (1) in vivo α-synuclein immunoreactivity has the potential as a pathological biomarker for PD; (2) anti-phosphorylated α-synuclein antibody consistently has higher specificity than anti-native α-synuclein antibody; and (3) skin biopsy examination using anti-phosphorylated α-synuclein antibody has the best diagnostic accuracy, although feasibility remains an important issue. © 2019 International Parkinson and Movement Disorder Society.
先前的研究已经探讨了体内异常 α-突触核蛋白沉积作为 PD 的潜在病理生物标志物的可能性，这些研究的参与者较少，报告的诊断准确性也不同。在这里，我们通过系统评价和荟萃分析旨在证实体内 α-突触核蛋白沉积在 PD 中的诊断价值，特别强调确定最适合检查的组织，并评估是否应使用抗天然 α-突触核蛋白或抗磷酸化 α-突触核蛋白抗体。我们于 2018 年 12 月 30 日对数据库进行了搜索。最终，我们纳入了 41 项病例对照研究，这些研究使用抗天然 α-突触核蛋白或抗磷酸化 α-突触核蛋白抗体在 PD 患者和对照组中检查了体内组织样本。使用单变量随机效应模型，抗天然 α-突触核蛋白抗体的合并敏感性和特异性（95%置信区间）为 0.54（0.49-0.60）和 0.72（0.68-0.76）用于胃肠道，0.76（0.60-0.89）和 0.60（0.43-0.74）用于皮肤。抗磷酸化 α-突触核蛋白抗体的合并敏感性和特异性（95%置信区间）为 0.43（0.37-0.48）和 0.82（0.78-0.86）用于胃肠道，0.76（0.69-0.82）和 1.00（0.98-1.00）用于皮肤，0.42（0.26-0.59）和 0.94（0.84-0.99）用于小唾液腺，0.66（0.51-0.79）和 0.96（0.86-1.00）用于颌下腺。在解释我们的结果时，应该注意到纳入研究之间存在普遍的异质性，但我们的分析表明：（1）体内 α-突触核蛋白免疫反应性具有作为 PD 的病理生物标志物的潜力；（2）抗磷酸化 α-突触核蛋白抗体的特异性始终高于抗天然 α-突触核蛋白抗体；（3）尽管皮肤活检检查使用抗磷酸化 α-突触核蛋白抗体具有最佳的诊断准确性，但可行性仍然是一个重要问题。
