A Panel of Autoantibodies Against Neural Proteins as Peripheral Biomarker for Pesticide-Induced Neurotoxicity
A Panel of Autoantibodies Against Neural Proteins as Peripheral Biomarker for Pesticide-Induced Neurotoxicity
复制标题
DOI：
10.1007/s12640-017-9793-y
复制
发表时间：
2018-02-01
影响因子：
3.7
通讯作者：
Abou-Donia, Mohamed B.
中科院分区：
文献类型：
--
作者：
Abd El Rahman, Heba Allah;Salama, Mohamed;Abou-Donia, Mohamed B.
在本研究中，我们筛选了长期暴露于农药混合物（主要由有机磷化合物（OP）和其他）的受试者的血清，并针对细胞骨架神经蛋白的自身抗体的存在开发了神经系统症状。OP具有由急性胆碱能危象引起的充分表征的临床特征。然而，这些化合物中的一些引起神经元变性和脱髓鞘，称为有机磷化合物诱导的迟发性神经毒性（OPIDN）和/或有机磷化合物诱导的慢性神经毒性（OPICN）。我们小组的研究已经证明了化学性脑损伤患者中存在针对细胞骨架神经蛋白的必需神经元和神经胶质蛋白的自身抗体。在这项研究中，我们筛选了50名农药暴露受试者和25名非暴露对照的血清，使用蛋白质印迹分析针对以下蛋白质：神经丝三联体蛋白（NFP）、微管蛋白、微管相关tau蛋白（Tau）、微管相关蛋白-2（MAP-2）、髓鞘碱性蛋白（MBP）、髓鞘相关糖蛋白（MAG）、胶质细胞酸性蛋白（GFAP）、钙-钙调蛋白激酶II（CaMK II）、神经胶质S100-B蛋白和α-突触核蛋白（SNCA）。血清反应性测量为任意化学发光单位。作为一个群体，暴露受试者在所有检查病例中的自身抗体反应性水平显著较高。与健康人相比，受试者的抗神经蛋白的自身抗体的增加倍数以降序如下：MBP，7.67，MAG 5.89，CaMKII 5.50，GFAP 5.1，TAU 4.96，MAP 2 4.83，SNCA 4.55，NFP 4.55，S-100 B 2.43，和微管蛋白1.78。这项研究表明，血清中存在的中枢神经系统特异性蛋白质的自身抗体在一组农民长期暴露于农药谁开发神经系统的体征和神经损伤的症状。这些自身抗体可用作OP诱导的神经毒性的未来诊断/治疗靶点。
In the present study, we screened the sera of subjects chronically exposed to mixtures of pesticides (composed mainly of organophosphorus compounds (OPs) and others) and developed neurological symptoms for the presence of autoantibodies against cytoskeletal neural proteins. OPs have a well-characterized clinical profile resulting from acute cholinergic crisis. However, some of these compounds cause neuronal degeneration and demyelination known as organophosphorus compound-induced delayed neurotoxicity (OPIDN) and/or organophosphorus compound-induced chronic neurotoxicity (OPICN). Studies from our group have demonstrated the presence of autoantibodies to essential neuronal and glial proteins against cytoskeletal neural proteins in patients with chemical-induced brain injury. In this study, we screened the serum of 50 pesticide-exposed subjects and 25 non-exposed controls, using Western blot analysis against the following proteins: neurofilament triplet proteins (NFPs), tubulin, microtubule-associated tau proteins (Tau), microtubule-associated protein-2 (MAP-2), myelin basic protein (MBP), myelin-associated glycoprotein (MAG), glial fibrillary acidic protein (GFAP), calcium-calmodulin kinase II (CaMKII), glial S100-B protein, and alpha-synuclein (SNCA). Serum reactivity was measured as arbitrary chemiluminescence units. As a group, exposed subjects had significantly higher levels of autoantibody reactivity in all cases examined. The folds of increase in of autoantibodies against neural proteins of the subjects compared to healthy humans in descending order were as follows: MBP, 7.67, MAG 5.89, CaMKII 5.50, GFAP 5.1, TAU 4.96, MAP2 4.83, SNCA 4.55, NFP 4.55, S-100B 2.43, and tubulin 1.78. This study has demonstrated the presence of serum autoantibodies to central nervous system-specific proteins in a group of farmers chronically exposed to pesticides who developed neurological signs and symptoms of neural injury. These autoantibodies can be used as future diagnostic/therapeutic target for OP-induced neurotoxicity.