Division of Health Research, Centre for Health Science, University of the Highlands and Islands, UK.
Department of Medicine and Dentistry, University of Aberdeen, UK.
Schizophr Bull. 2018 Oct 17;44(6):1341-1349. doi: 10.1093/schbul/sbx175.
A recent genome-wide association (GWA) study confirmed 108 genetic loci that were strongly associated with schizophrenia. Fifteen schizophrenia-associated genes were selected for this study based on a number of selection criteria including their high expression in both brain tissues and B-lymphocyte cells. We aimed to investigate whether individuals with schizophrenia showed different levels of plasma IgG antibodies against protein-derived fragments encoded by these 15 genes. A total of 356 plasma samples were used to analyze circulating IgG antibodies against 18 target peptide antigens using an in-house enzyme-linked immunosorbent assay. Of 18 antigens tested, 6 (derived from DPYD, MAD1L1, ZNF804A, DRD2, TRANK1, and MMP16, respectively) showed increased IgG levels and 3 (derived from TSNARE1, TCF4, and VRK2, respectively) showed decreased IgG levels in patients with schizophrenia compared with control subjects. Receiver operating characteristic (ROC) curve analysis revealed that the anti-TRANK1 IgG assay had the area under the ROC curve of 0.68 (95% CI = 0.62-0.73), with the highest sensitivity of 20.7% against specificity of 95.2% among all 18 tests. There was no difference in positivity of anti-double strand DNA IgG between the patient group and the control group and no correlation between total IgG levels and each individual IgG level tested. Although risperidone treatment showed confounding effects on overall IgG levels in the circulation (combined P = .005), anti-TRANK1 IgG levels did not appear to be significantly affected (t = 1.358, P = .176). In conclusion, this study suggests that circulating anti-TRANK1 IgG is likely to serve as a biomarker for identification of a subgroup of schizophrenia.
一项最近的全基因组关联（GWA）研究证实了 108 个与精神分裂症强烈相关的遗传位点。基于包括在脑组织和 B 淋巴细胞中高表达在内的多项选择标准，从这些与精神分裂症相关的基因中选择了 15 个基因进行本研究。我们旨在研究精神分裂症患者是否表现出针对这 15 个基因编码的蛋白质衍生片段的不同水平的血浆 IgG 抗体。使用内部酶联免疫吸附试验分析了 356 个血浆样本，以分析针对 18 个靶肽抗原的循环 IgG 抗体。在测试的 18 种抗原中，有 6 种（分别来自 DPYD、MAD1L1、ZNF804A、DRD2、TRANK1 和 MMP16）在精神分裂症患者中显示出 IgG 水平升高，而 3 种（分别来自 TSNARE1、TCF4 和 VRK2）显示出 IgG 水平降低与对照组相比，在精神分裂症患者中。受试者工作特征（ROC）曲线分析显示，抗 TRANK1 IgG 检测的 ROC 曲线下面积为 0.68（95%CI=0.62-0.73），在所有 18 项检测中，其敏感性最高为 20.7%，特异性为 95.2%。患者组和对照组之间抗双链 DNA IgG 的阳性率没有差异，并且总 IgG 水平与每个个体 IgG 水平之间没有相关性。虽然利培酮治疗对循环中的总 IgG 水平有混杂影响（合并 P=0.005），但抗 TRANK1 IgG 水平似乎没有受到显著影响（t=1.358，P=0.176）。总之，这项研究表明，循环中的抗 TRANK1 IgG 可能作为精神分裂症亚群识别的生物标志物。
