Comparable Autoantibody Serum Levels against Amyloid- and Inflammation-Associated Proteins in Parkinson’s Disease Patients and Controls

Naturally occurring autoantibodies (NAbs) against a number of potentially disease-associated cellular proteins, including Amyloid-beta1–42 (Abeta1–42), Alpha-synuclein (Asyn), myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), and S100 calcium binding protein B (S100B) have been suggested to be associated with neurodegenerative disorders, in particular Alzheimer’s (AD) and Parkinson’s disease (PD). Whereas the (reduced) occurrence of specific NAbs in AD is widely accepted, previous literature examining the relation of these NAb titres between PD patients and controls, as well as comparing these levels with demographic and clinical parameters in PD patients have produced inconsistent findings. We therefore aimed, in a cross-sectional approach, to determine serum titres of the above NAbs in a cohort of 93 PD patients (31 of them demented) and 194 controls. Levels were correlated with demographic and clinical variables, cerebrospinal fluid Abeta1–42, total tau and phospho-tau levels, as well as with single nucleotide polymorphisms (SNPs) of genes which either have been reported to influence the immune system, the amyloid cascade or the occurrence of PD (ApoE, GSK3B, HLA-DRA, HSPA5, SNCA, and STK39). The investigated NAb titres were neither significantly associated with the occurrence of PD, nor with demographic and clinical parameters, neurodegenerative markers or genetic variables. These results argue against a major potential of blood-borne parameters of the adaptive immune system to serve as trait or state markers in PD.

针对多种潜在疾病相关细胞蛋白的天然自身抗体（naturally occurring autoantibodies，NAbs），包括β淀粉样蛋白1-42（Amyloid-beta1–42，Aβ₁₋₄₂）、α-突触核蛋白（Alpha-synuclein，Asyn）、髓鞘碱性蛋白（myelin basic protein，MBP）、髓鞘少突胶质细胞糖蛋白（myelin oligodendrocyte glycoprotein，MOG）以及S100钙结合蛋白B（S100 calcium binding protein B，S100B），已被提示与神经退行性疾病相关，尤其是阿尔茨海默病（Alzheimer’s disease，AD）和帕金森病（Parkinson’s disease，PD）。尽管阿尔茨海默病患者体内特定天然自身抗体的水平降低现象已被广泛认可，但此前针对帕金森病患者与健康对照者之间此类天然自身抗体滴度的关联研究，以及在帕金森病患者中比较这些水平与人口统计学及临床参数的研究，所得结果并不一致。因此，本研究采用横断面研究方法，旨在检测93例帕金森病患者（其中31例伴有痴呆）及194名健康对照者血清中上述天然自身抗体的滴度。研究同时将抗体水平与人口统计学及临床变量、脑脊液中β淀粉样蛋白1-42、总tau蛋白及磷酸化tau蛋白水平，以及据报道可影响免疫系统、淀粉样蛋白级联反应或帕金森病发生的相关基因的单核苷酸多态性（single nucleotide polymorphisms，SNPs）进行了关联分析，这些基因包括ApoE、GSK3B、HLA-DRA、HSPA5、SNCA及STK39。本研究检测的天然自身抗体滴度，既未与帕金森病的发生显著相关，也未与人口统计学及临床参数、神经退行性标志物或遗传变量存在显著关联。上述结果提示，血液来源的适应性免疫系统参数作为帕金森病特征性或状态性标志物的潜在价值有限。