Heinzel Sebastian, Gold Maike, Deuschle Christian, Bernhard Felix, Maetzler Walter, Berg Daniela, Dodel Richard
Department of Neurodegeneration, Hertie Institute for Clinical Brain Research (HIH), University of Tuebingen, Tuebingen, Germany.
Department of Neurology, Philipps-University Marburg, Marburg, Germany.
PLoS One. 2014 Dec 3;9(12):e114566. doi: 10.1371/journal.pone.0114566. eCollection 2014.
Alpha-synuclein (α-Syn) plays a pivotal role in the pathophysiology of Parkinson's disease (PD), which can partly be modulated by innate and adaptive immune functions, and vice versa. Here, naturally occurring α-Syn autoantibodies (α-Syn-nAbs) may be effective against α-Syn pathoetiology and may serve as a PD biomarker. However, serum and cerebrospinal fluid α-Syn-nAbs levels still lack consistent evidence as required for a reliable PD biomarker. Serum and cerebrospinal fluid α-Syn-nAbs levels of 66 PD patients and 69 healthy controls were assessed using a validated ELISA assay. Moreover, potential sources of error variance including unspecific ELISA background signals, free serum hemoglobin concentrations, α-Syn plate coating procedures, and differences in α-Syn-nAbs standards, were investigated. PD patients and controls did not differ in serum (p = .49) nor cerebrospinal fluid (p = .29) α-Syn-nAbs levels. Interestingly, free serum hemoglobin concentrations were negatively correlated with α-Syn-nAbs levels in controls (Spearman ρ = -.41, p<.001), but not in PD patients (ρ = .16, p = .21). ELISA α-Syn plate coating procedures impacted inter-assay variability (same day coating: 8-16%; coating on different days: 16-58%). α-Syn-nAbs standards from different purification batches differed regarding optical density measured in ELISAs suggesting differences in α-Syn affinity. While α-Syn-nAbs levels may represent a potential PD biomarker, several methodological issues have to be considered to increase reproducibility of α-Syn-nAbs findings. Further studies using standardized protocols minimizing sources of error variance may be necessary to establish a reliable PD α-Syn-nAbs biomarker.
α-突触核蛋白（α-Syn）在帕金森病（PD）的病理生理学中起关键作用，其可部分受先天性和适应性免疫功能调节，反之亦然。在此，天然存在的α-Syn自身抗体（α-Syn-nAbs）可能对α-Syn发病机制有效，并且可作为PD的生物标志物。然而，血清和脑脊液α-Syn-nAbs水平仍缺乏作为可靠PD生物标志物所需的一致证据。使用经过验证的酶联免疫吸附测定（ELISA）法评估了66例PD患者和69例健康对照的血清和脑脊液α-Syn-nAbs水平。此外，还研究了误差方差的潜在来源，包括非特异性ELISA背景信号、游离血清血红蛋白浓度、α-Syn板包被程序以及α-Syn-nAbs标准品的差异。PD患者和对照组在血清（p = 0.49）和脑脊液（p = 0.29）α-Syn-nAbs水平上无差异。有趣的是，游离血清血红蛋白浓度与对照组的α-Syn-nAbs水平呈负相关（Spearman ρ = -0.41，p < 0.001），但在PD患者中无相关性（ρ = 0.16，p = 0.21）。ELISA α-Syn板包被程序影响了批间变异性（同一天包被：8 - 16%；不同天包被：16 - 58%）。来自不同纯化批次的α-Syn-nAbs标准品在ELISA中测得的光密度不同，表明α-Syn亲和力存在差异。虽然α-Syn-nAbs水平可能代表一种潜在的PD生物标志物，但必须考虑几个方法学问题以提高α-Syn-nAbs研究结果的可重复性。使用标准化方案最大限度减少误差方差来源的进一步研究可能对于建立可靠的PD α-Syn-nAbs生物标志物是必要的。
