诊断和监测帕金森病进展的生物标志物甚为需要，目前，大部分的研究集中在α-突触核蛋白 (α-Syn)。它是一种涉及帕金森病发病机理的蛋白质，作为一种潜在的生物标志物，有时与临床结果并不一致。近期在帕金森病患者的血清中检测到了自身存在的抗α-Syn自身抗体。马尔堡菲利普大学神经科的Daniela Besong-Agbo博士等人进行了一项研究，研究结果在线发表在2012年12月19日的Neurology杂志上。研究结果发现：相较AD患者与健康对照人群，帕金森病患者的α-Syn-nAbs水平降低。
研究人员建立并验证了血清标本量化检测的α-Syn 自然发生自身抗体（α-Syn-nAbs）的ELISA法。使用这种新建的ELISA方法分析来自62位帕金森病患者的血清标本和46位健康对照（HC）及42位阿尔茨海默病（AD）患者。另外，还测定了血清内源性α-Syn水平。
研究结果显示：各观察组α-Syn-nAbs 水平存在显著差异(p = 0.005; Kruskal-Wallis测试法)。相较正常对照组(p < 0.05; Dunn多重比较)和AD患者(p < 0.05)，帕金森病患者的α-Syn-nAbs 水平显著较低。
该研究发现：使用验证良好的方法，相较AD患者与健康对照人群，帕金森病患者的α-Syn-nAbs水平降低。该方法还无法用作可靠区分帕金森病与健康对照的可靠工具。需要进一步的研究评估α-Syn-nAbs能否作为帕金森病患者的一个生物标志物。(生物谷Bioon.com)
DOI:10.1212/WNL.0b013e31827b90d1
PMC:
PMID:
Naturally occurring α-synuclein autoantibody levels are lower in patients with Parkinson disease
Besong-Agbo D, Wolf E, Jessen F, Oechsner M, Hametner E, Poewe W, Reindl M, Oertel WH, Noelker C, Bacher M, Dodel R.
OBJECTIVE:Biomarkers are required for the diagnosis and monitoring of disease progression in Parkinson disease (PD). To date, most studies have concentrated on α-synuclein (α-Syn), a protein involved in Parkinson disease pathogenesis, as a potential biomarker, with inconsistent outcomes. Recently, naturally occurring autoantibodies against α-Syn (α-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 α-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 α-Syn were measured. RESULTS:There was a significant difference in α-Syn-nAbs levels between the investigated groups (p = 0.005; Kruskal-Wallis test). Levels of α-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 α-Syn-nAbs levels did not correlate with age, Hoehn & Yahr status, or duration of disease. Endogenous α-Syn had no influence on α-Syn-nAbs levels in sera. CONCLUSIONS:Using a well-validated assay, we detected reduced α-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 α-Syn-nAbs as a biomarker in PD
