Brain-reactive autoantibodies are nearly ubiquitous in human sera and may be linked to pathology in the context of blood-brain barrier breakdown
Brain-reactive autoantibodies are nearly ubiquitous in human sera and may be linked to pathology in the context of blood-brain barrier breakdown
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DOI：
10.1016/j.brainres.2010.05.038
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发表时间：
2010-07-23
期刊：
影响因子：
2.9
通讯作者：
Nagele, Robert G.
中科院分区：
文献类型：
--
作者：
Levin, Eli C.;Acharya, Nimish K.;Nagele, Robert G.
先前的研究报道了与死后阿尔茨海默病（AD）大脑细胞结合的抗体，而在健康、年龄匹配的对照者的大脑中很少观察到这种情况。这意味着 AD 个体的血清中存在脑反应性自身抗体，并且可以进入脑间质。为了研究这种可能性，我们通过免疫组织化学和蛋白质印迹分析确定了 AD 患者、其他神经退行性疾病患者、年龄匹配的非痴呆对照者和健康年轻人血清中脑反应性抗体的患病率。令人惊讶的是，西方分析显示，92% 的测试人类血清含有脑反应性自身抗体。当使用血清探测人、猪或大鼠脑膜蛋白的蛋白质印迹时，检测到许多大小相当的蛋白质靶标，这表明跨物种反应性。虽然人类血清中几乎普遍存在脑反应性自身抗体，但一些自身抗体似乎与年龄或疾病有关。此外，抗体与脑组织成分（尤其是神经元表面）结合的强度与血清自身抗体谱的相关性比与年龄或神经退行性疾病的存在更密切相关。然而，虽然对照大脑中的血脑屏障 (BBB) 保持完整，但 AD 大脑中 BBB 破坏很常见。结果表明，人血清中脑反应性抗体的存在率很高，在 BBB 受损的常见背景下，我们提出这些抗体可能有助于 AD 和其他神经退行性疾病的起始和/或发病。 (C) 2010 Elsevier B.V. 保留所有权利。
Previous studies have reported antibodies bound to cells in postmortem Alzheimer's disease (AD) brains, which are only rarely observed in the brains of healthy, age-matched controls. This implies that brain-reactive autoantibodies exist in the sera of AD individuals and can gain access to the brain interstitium. To investigate this possibility, we determined the prevalence of brain-reactive antibodies in sera from AD patients, patients with other neurodegenerative diseases, age-matched, non-demented controls and healthy younger individuals via immunohistochemistry and western blot analysis. Surprisingly, western analyses revealed that 92% of all human sera tested contain brain-reactive autoantibodies. When sera were used to probe western blots of human, pig, or rat brain membrane proteins, a number of comparably-sized protein targets were detected, suggesting cross-species reactivity. While the presence of brain-reactive autoantibodies was nearly ubiquitous in human sera, some autoantibodies appeared to be associated with age or disease. Furthermore, the intensity of antibody binding to brain tissue elements, especially the surfaces of neurons, correlated more closely to the serum's autoantibody profile than to age or the presence of neurodegenerative disease. However, while the blood brain barrier (BBB) in control brains remained intact, BBB breakdown was common in AD brains. Results suggest a high prevalence of brain-reactive antibodies in human sera which, in the common context of BBB compromise, leads us to propose that these antibodies may contribute to the initiation and/or pathogenesis of AD and other neurodegenerative diseases. (C) 2010 Elsevier B.V. All rights reserved.