Department of Neurology, Beaumont Research Institute, Beaumont Health System, 3811 West Thirteen Mile Road, Royal Oak, MI 48073, USA.
Department of Neurology, Beaumont Research Institute, Beaumont Health System, 3811 West Thirteen Mile Road, Royal Oak, MI 48073, USA.
Int Immunopharmacol. 2015 Oct;28(2):1108-12. doi: 10.1016/j.intimp.2015.08.022. Epub 2015 Aug 30.
The therapeutic effects of intravenous immunoglobulin (IVIG) products were recently studied in Alzheimer's disease (AD) patients. Pilot studies produced encouraging results but phase II and III trials gave disappointing results; a further study is in progress. IVIG products contain antibodies to tau protein, the main component of neurofibrillary tangles (NFTs). The tau used to detect IVIG's anti-tau antibodies in previous studies was non-phosphorylated recombinant human tau-441, but NFT-associated tau is extensively phosphorylated. The objective of this study was to determine if various IVIG products contain specific antibodies to phosphorylated tau (anti-pTau antibodies). ELISAs were used to evaluate binding of six IVIG products to a 12 amino acid peptide, tau 196-207, which was phosphorylated ("pTau peptide") or non-phosphorylated ("non-pTau peptide") at Serine-199 and Serine-202. Both amino acid residues are phosphorylated in AD NFTs. Each IVIG's "anti-pTau antibody ratio" was calculated by dividing its binding to the pTau peptide by its binding to the non-pTau peptide. Seven experiments were performed and data were pooled, with each experiment contributing one data point from each IVIG product. Mean anti-pTau antibody ratios greater than 1.0, suggesting specific antibodies to phosphorylated tau, were found for three IVIG products. Because administration of antibodies to phosphorylated tau has been found to reduce tau-associated pathology in transgenic mouse models of tauopathy, increasing the levels of anti-pTau antibodies, together with other selected antibodies such as anti-Aβ, in IVIG might increase its ability to slow AD's progression.
静脉注射免疫球蛋白（IVIG）产品在阿尔茨海默病（AD）患者中的治疗效果最近得到了研究。初步研究结果令人鼓舞，但 II 期和 III 期试验结果令人失望；进一步的研究正在进行中。IVIG 产品含有针对tau 蛋白的抗体，tau 蛋白是神经原纤维缠结（NFTs）的主要成分。以前的研究中用于检测 IVIG 抗 tau 抗体的 tau 是未磷酸化的重组人 tau-441，但 NFT 相关的 tau 广泛磷酸化。本研究的目的是确定各种 IVIG 产品是否含有针对磷酸化 tau（抗 pTau 抗体）的特异性抗体。ELISA 用于评估六种 IVIG 产品与 12 个氨基酸肽段 tau 196-207 的结合情况，该肽段在丝氨酸 199 和丝氨酸 202 处发生磷酸化（“pTau 肽段”）或未磷酸化（“非 pTau 肽段”）。这两个氨基酸残基在 AD NFTs 中都发生了磷酸化。每个 IVIG 的“抗 pTau 抗体比”通过其与 pTau 肽段的结合除以其与非 pTau 肽段的结合来计算。进行了七项实验，数据汇总，每项实验从每种 IVIG 产品贡献一个数据点。发现三种 IVIG 产品的抗 pTau 抗体比值大于 1.0，提示对磷酸化 tau 具有特异性抗体。由于向 tau 病变的转基因小鼠模型中给药针对磷酸化 tau 的抗体已被发现可减少 tau 相关病理学，因此增加 IVIG 中抗 pTau 抗体的水平，以及其他选定的抗体（如抗 Aβ），可能会增加其减缓 AD 进展的能力。
