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.
Bibliographical noteWe thank the patients and healthy volunteers for their support and participation. We also thank NHS Grampian for sample collection as well as Dr Mark Coulson from Inverness College, University of the Highlands and Islands (UHI) and our colleagues at UHI Division of Health Research for their supportive work. This study was supported by the Schizophrenia Association of Great Britain, Bangor, UK. The authors declared that they had no conflict of interests.