Potential utility of autoantibodies as blood-based biomarkers for early detection and diagnosis of Parkinson's disease
Potential utility of autoantibodies as blood-based biomarkers for early detection and diagnosis of Parkinson's disease
复制标题
自身抗体作为血液生物标记物在早期检测和诊断帕金森病方面的潜在作用
DOI：
10.1016/j.imlet.2015.09.010
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发表时间：
2015-11-01
影响因子：
4.4
通讯作者：
Nagele, Robert G.
中科院分区：
文献类型：
--
作者：
DeMarshall, Cassandra A.;Han, Min;Nagele, Robert G.
简介： 非常需要识别帕金森病 (PD) 易于获取的血液生物标志物，这有助于准确的早期检测和诊断。这一进步将允许早期患者治疗和纳入临床试验，这两者都将极大地促进 PD 新疗法的开发。 方法：使用含有 9,486 个潜在抗原靶标的人类蛋白微阵列对总共 398 名受试者（包括来自帕金森病的 Deprenyl 和生育酚抗氧化治疗 (DATATOP) 研究的 103 名早期 PD 受试者）的血清进行筛选，以识别可能用作 PD 生物标志物的自身抗体。使用随机森林识别并测试了一组在早期 PD 中患病率较高的选定自身抗体，以检验其区分早期 PD 受试者与对照以及患有其他神经退行性疾病和非神经退行性疾病的个体的能力。 结果：结果表明，一组选定的血源性自身抗体生物标志物可以区分早期 PD 受试者（诊断置信度为 90%）与年龄和性别匹配的对照，总体准确度为 87.9%，灵敏度为94.1%，特异性为 85.5%。这些生物标志物还能够以 97.5% 的总体准确度区分早期 PD 患者和更晚期（轻中度）PD 患者，并且可以将早期 PD 受试者与其他神经系统疾病（例如阿尔茨海默病和多发性硬化症）和非神经系统疾病（例如乳腺癌）患者区分开来。结论：这些结果首次证明，一组选定的自身抗体可能被证明是有效的。用于诊断早期 PD 的血液生物标志物。 (C) 2015 年作者。由 Elsevier B.V. 出版
Introduction: There is a great need to identify readily accessible, blood-based biomarkers for Parkinson's disease (PD) that are useful for accurate early detection and diagnosis. This advancement would allow early patient treatment and enrollment into clinical trials, both of which would greatly facilitate the development of new therapies for PD.Methods: Sera from a total of 398 subjects, including 103 early-stage PD subjects derived from the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) study, were screened with human protein microarrays containing 9,486 potential antigen targets to identify autoantibodies potentially useful as biomarkers for PD. A panel of selected autoantibodies with a higher prevalence in early-stage PD was identified and tested using Random Forest for its ability to distinguish early-stage PD subjects from controls and-from individuals with other neurodegenerative and non-neurodegenerative diseases.Results: Results demonstrate that a panel of selected, blood-borne autoantibody biomarkers can distinguish early-stage PD subjects (90% confidence in diagnosis) from age- and sex-matched controls with an overall accuracy of 87.9%, a sensitivity of 94.1% and specificity of 85.5%. These biomarkers were also capable of differentiating patients with early-stage PD from those with more advanced (mild-moderate) PD with an overall accuracy of 97.5%, and could distinguish subjects with early-stage PD from those with other neurological (e.g., Alzheimer's disease and multiple sclerosis) and non-neurological (e.g., breast cancer) diseases.Conclusion: These results demonstrate, for the first time, that a panel of selected autoantibodies may prove to be useful as effective blood-based biomarkers for the diagnosis of early-stage PD. (C) 2015 The Authors. Published by Elsevier B.V.