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在中国人群中,精神分裂症患者的抗TSNARE1 IgG血浆水平存在性别差异。

Anti-TSNARE1 IgG plasma levels differ by sex in patients with schizophrenia in a Chinese population.

作者信息

Li Chan, Whelan Ruth, Yang Hua, Jiang Yaling, Qiu Chaosen, Meng Qingyong, Wei Jun

机构信息

Laboratory for Nursing Science & Institute of Laboratory Medicine, Guangdong Medical University, Dongguan, China.

Institute of Health Research & Innovation, University of the Highlands & Islands, Inverness, UK.

出版信息

FEBS Open Bio. 2019 Oct;9(10):1705-1712. doi: 10.1002/2211-5463.12704. Epub 2019 Sep 4.

Abstract

It was recently reported that levels of plasma IgG antibodies against peptide antigens derived from proteins encoded by schizophrenia-associated genes are altered in individuals with schizophrenia treated with antipsychotics. This study aimed to replicate the initial finding in antipsychotic-naïve patients with first-episode schizophrenia and to explore the possible mechanism by which immune tolerance of B cells may be altered in this disease. A total of 408 case-control plasma samples were collected for analysis of circulating IgG antibodies against fragments derived from TCF4, TSNARE1, ZNF804A, TRANK1, ERCC4, DPYD and CD25 using an in-house ELISA. The Mann-Whitney U-test revealed that patients with schizophrenia had a significant change in plasma anti-TSNARE1 and anti-CD25 IgG levels; male patients mainly contributed to the increased levels of anti-TSNARE1 IgG and anti-CD25 IgG. Receiver operating characteristic (ROC) curve analysis revealed that the anti-TSNARE1 IgG assay had an area under the ROC curve of 0.625 with a sensitivity of 15.7% and a specificity of 95.2%. Work on a B-cell model revealed that TRANK1-derived antigen treatments could enhance the proportions of CD83+ cells and apoptotic B cells when compared with TSNARE1-derived antigen and vehicle treatment. We conclude that there is a gender difference in autoimmune responses in schizophrenia and suggest that anti-TSNARE1 IgG may be indicative of schizophrenia in a subgroup of male patients.

摘要

最近有报道称,在接受抗精神病药物治疗的精神分裂症患者中,针对精神分裂症相关基因编码蛋白衍生的肽抗原的血浆IgG抗体水平发生了改变。本研究旨在在初发精神分裂症未使用过抗精神病药物的患者中重复这一初步发现,并探讨在该疾病中B细胞免疫耐受性可能发生改变的潜在机制。共收集了408份病例对照血浆样本,使用内部酶联免疫吸附测定法(ELISA)分析针对源自TCF4、TSNARE1、ZNF804A、TRANK1、ERCC4、DPYD和CD25的片段的循环IgG抗体。曼-惠特尼U检验显示,精神分裂症患者的血浆抗TSNARE1和抗CD25 IgG水平有显著变化;男性患者主要导致抗TSNARE1 IgG和抗CD25 IgG水平升高。受试者工作特征(ROC)曲线分析显示,抗TSNARE1 IgG检测的ROC曲线下面积为0.625,灵敏度为15.7%,特异性为95.2%。对B细胞模型的研究表明,与源自TSNARE1的抗原和赋形剂处理相比,源自TRANK1的抗原处理可提高CD83+细胞和凋亡B细胞的比例。我们得出结论,精神分裂症患者的自身免疫反应存在性别差异,并表明抗TSNARE1 IgG可能在男性患者亚组中指示精神分裂症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1231/6768289/de3e376c964e/FEB4-9-1705-g001.jpg

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