Naturally occurring α-synuclein autoantibody levels are lower in patients with Parkinson disease

Naturally occurring α-synuclein autoantibody levels are lower in patients with Parkinson disease
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DOI:
10.1212/wnl.0b013e31827b90d1
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发表时间:
2013-01-01
期刊:
影响因子:
9.9
通讯作者:
Dodel, Richard
Dodel, Richard
中科院分区:
医学1区
文献类型:
--
作者:
Besong-Agbo, Daniela;Wolf, Elias;Dodel, Richard

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目的:帕金森病(PD)的诊断和病情监测需要生物标志物。迄今为止,大多数研究都集中在α-突触核蛋白(α-Syn),一种参与帕金森病发病机制的蛋白质,作为一种潜在的生物标志物,结果不一致。最近,在PD患者的血清中检测到天然存在的抗α-Syn的自身抗体(α-Syn-nAbs)。他们代表了一个假定的诊断标志物PD.Methods:我们建立并验证了ELISA定量α-Syn-nAbs血清样品。我们分析了62例PD患者,46名健康对照(HC)和42例阿尔茨海默病(AD)患者的血清样本,使用这种新建立的ELISA。此外,内源性alpha-Syn.Results血清水平进行了测量:有一个显着的差异,在研究组之间的alpha-Syn-nAbs水平(p = 0.005; Kruskal-Wallis检验)。与HC(p < 0.05; Dunn多重比较事后检验)或AD患者(p,0.05)相比,PD患者中的α-Syn-nAb水平显著较低。此外,我们没有发现AD和HC患者之间的差异。与HC相比,该检测方法对PD患者的敏感性和特异性分别为85%和25%。α-Syn-nAbs水平与年龄、Hoehn & Yahr状态或疾病持续时间无关。内源性α-Syn没有影响alpha-Syn-nAbs的水平在sero.Conclusions:使用一个经过充分验证的测定,我们检测到降低的alpha-Syn-nAbs水平与AD和HC患者相比,PD患者。该测定未达到用作诊断工具以可靠区分PD与HC的标准。需要进一步的研究来评估alpha-Syn-nAb作为PD中的生物标志物。神经病学(R)2013;80:169-175
Objective: Biomarkers are required for the diagnosis and monitoring of disease progression in Parkinson disease (PD). To date, most studies have concentrated on alpha-Synuclein (alpha-Syn), a protein involved in Parkinson disease pathogenesis, as a potential biomarker, with inconsistent outcomes. Recently, naturally occurring autoantibodies against alpha-Syn (alpha-Syn-nAbs) have been detected in the serum of patients with PD. They represent a putative diagnostic marker for PD.Methods: We established and validated an ELISA to quantify alpha-Syn-nAbs in serum samples. We analyzed serum samples from 62 patients with PD, 46 healthy controls (HC), and 42 patients with Alzheimer disease (AD) using this newly established ELISA. Additionally, serum levels of endogenous alpha-Syn were measured.Results: There was a significant difference in alpha-Syn-nAbs levels between the investigated groups (p = 0.005; Kruskal-Wallis test). Levels of alpha-Syn-nAbs were significantly lower in patients with PD compared to HC (p < 0.05; Dunn multiple comparison post hoc test) or patients with AD (p, 0.05). Furthermore, we detected no difference between patients with AD and HC. The sensitivity and specificity of the assay for patients with PD vs HC were 85% and 25%, respectively. The alpha-Syn-nAbs levels did not correlate with age, Hoehn & Yahr status, or duration of disease. Endogenous alpha-Syn had no influence on alpha-Syn-nAbs levels in sera.Conclusions: Using a well-validated assay, we detected reduced alpha-Syn-nAbs levels in patients with PD compared to patients with AD and HC. The assay did not achieve criteria for use as a diagnostic tool to reliably distinguish PD from HC. Further studies are needed to assess alpha-Syn-nAbs as a biomarker in PD. Neurology (R) 2013;80:169-175