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Brain antibodies in the cortex and blood of people with schizophrenia and controls

机译:精神分裂症和对照人群的皮质和血液中的脑抗体

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摘要

The immune system is implicated in the pathogenesis of schizophrenia, with elevated proinflammatory cytokine mRNAs found in the brains of ~40% of individuals with the disorder. However, it is not clear if antibodies (specifically immunoglobulin-γ (IgG)) can be found in the brain of people with schizophrenia and if their abundance relates to brain inflammatory cytokine mRNA levels. Therefore, we investigated the localization and abundance of IgG in the frontal cortex of people with schizophrenia and controls, and the impact of proinflammatory cytokine status on IgG abundance in these groups. Brain IgGs were detected surrounding blood vessels in the human and non-human primate frontal cortex by immunohistochemistry. IgG levels did not differ significantly between schizophrenia cases and controls, or between schizophrenia cases in ‘high’ and ‘low’ proinflammatory cytokine subgroups. Consistent with the existence of IgG in the parenchyma of human brain, mRNA and protein of the IgG transporter (FcGRT) were present in the brain, and did not differ according to diagnosis or inflammatory status. Finally, brain-reactive antibody presence and abundance was investigated in the blood of living people. The plasma of living schizophrenia patients and healthy controls contained antibodies that displayed positive binding to Rhesus macaque cerebellar tissue, and the abundance of these antibodies was significantly lower in patients than controls. These findings suggest that antibodies in the brain and brain-reactive antibodies in the blood are present under normal circumstances.
机译:免疫系统与精神分裂症的发病机制有关,在约40%患有这种疾病的人的大脑中发现了较高的促炎细胞因子mRNA。但是,尚不清楚在精神分裂症患者的大脑中是否可以找到抗体(特别是免疫球蛋白-γ(IgG)),以及它们的丰度是否与脑炎性细胞因子mRNA水平有关。因此,我们调查了精神分裂症和对照人群额叶皮质中IgG的定位和含量,以及这些组中促炎细胞因子状态对IgG含量的影响。通过免疫组织化学在人和非人的灵长类动物额叶皮层中的血管周围检测到脑IgG。精神分裂症病例与对照之间,或“高”和“低”促炎细胞因子亚组的精神分裂症病例之间,IgG水平无显着差异。与人脑实质中IgG的存在相一致,脑中存在IgG转运蛋白(FcGRT)的mRNA和蛋白,并且根据诊断或炎症状态没有差异。最后,研究了活人血液中脑反应性抗体的存在和丰度。存活的精神分裂症患者和健康对照组的血浆中含有与猕猴小脑组织呈阳性结合的抗体,患者中这些抗体的丰度明显低于对照组。这些发现表明在正常情况下存在脑中的抗体和血液中的脑反应性抗体。

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