Decrease in plasma levels of α-synuclein is evident in patients with Parkinson's disease after elimination of heterophilic antibody interference.
Decrease in plasma levels of α-synuclein is evident in patients with Parkinson's disease after elimination of heterophilic antibody interference.
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DOI：
10.1371/journal.pone.0123162
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
El-Agnaf OM
中科院分区：
文献类型：
--
作者：
Ishii R;Tokuda T;Tatebe H;Ohmichi T;Kasai T;Nakagawa M;Mizuno T;El-Agnaf OM
大量的生化、病理和遗传学证据表明，α-突触核蛋白(A-SYN)是帕金森病(PD)发病机制中的主要分子。我们曾报道PD患者脑脊液(CSF)中总A-syn水平下降，提示脑脊液(CSF)和血浆中A-syn可作为诊断PD的生物标志物。在我们的报告之后，相当多的研究调查了脑脊液和血液中A-SYN的水平，但报告了不确定的结果。这种差异通常不仅归因于在ELISA中使用不同的抗体，而且还归因于溶血的干扰。本研究采用自制的夹心ELISA法，检测了30例PD患者和58例年龄匹配的对照组脑脊液和血浆中A-syn水平。因此，我们发现HA干扰了A-SYN的ELISA测定，因此被认为是A-SYN ELISA中的一个重要混杂因素。HA在A-SYN ELISA中产生的虚假夸大信号在血浆样本中比在脑脊液样本中更明显。在排除HA干扰后，发现溶血对我们的A-SYN ELISA获得的信号没有显著影响。此外，在用HA抑制剂消除HA干扰后，PD组的血浆A-SYN水平显著低于对照组。我们的结果表明，HA是A-SYN ELISA中应控制的主要混杂因素，如果排除HA干扰后对血浆A-SYN进行适当的定量，则A-SYN可能成为诊断PD的有用生物标记物。
There is substantial biochemical, pathological, and genetic evidence that α-synuclein (A-syn) is a principal molecule in the pathogenesis of Parkinson disease (PD). We previously reported that total A-syn levels in cerebrospinal fluid (CSF), measured with the specific enzyme-linked immunosorbent assay (ELISA) developed by ourselves, were decreased in patients with PD, and suggested the usefulness of A-syn in CSF and plasma as a biomarker for the diagnosis of PD. After our report, a considerable number of studies have investigated the levels A-syn in CSF and in blood, but have reported inconclusive results. Such discrepancies have often been attributed not only to the use of different antibodies in the ELISAs but also to interference from hemolysis. In this study we measured the levels of A-syn in CSF and plasma by using our own sandwich ELISA with or without heterophilic antibody (HA) inhibitor in 30 patients with PD and 58 age-matched controls. We thereby revealed that HA interfered with ELISA measurements of A-syn and are accordingly considered to be an important confounder in A-syn ELISAs. HA produced falsely exaggerated signals in A-syn ELISAs more prominently in plasma samples than in CSF samples. After elimination of HA interference, it was found that hemolysis did not have a significant effect on the signals obtained using our A-syn ELISA. Furthermore, plasma levels of A-syn were significantly lower in the PD group compared with the control group following elimination of HA interference with an HA inhibitor. Our results demonstrate that HA was a major confounder that should be controlled in A-syn ELISAs, and that plasma A-syn could be a useful biomarker for the diagnosis of PD if adequately quantified following elimination of HA interference.
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影响因子：
6.1
作者：
Foulds, P. G.;Yokota, O.;Thurston, A.;Davidson, Y.;Ahmed, Z.;Holton, J.;Thompson, J. C.;Akiyama, H.;Arai, T.;Hasegawa, M.;Gerhard, A.;Allsop, D.;Mann, D. M. A.
通讯作者：
Mann, D. M. A.
影响因子：
4.7
作者：
Papachroni KK;Ninkina N;Papapanagiotou A;Hadjigeorgiou GM;Xiromerisiou G;Papadimitriou A;Kalofoutis A;Buchman VL
通讯作者：
Buchman VL
影响因子：
5.3
作者：
Mollenhauer, Brit;Cullen, Valerie;Schlossmacher, Michael G.
通讯作者：
Schlossmacher, Michael G.
影响因子：
9.9
作者：
Besong-Agbo, Daniela;Wolf, Elias;Dodel, Richard
通讯作者：
Dodel, Richard
影响因子：
14.5
作者：
Hong, Zhen;Shi, Min;Zhang, Jing
通讯作者：
Zhang, Jing