Study of Novel Autoantibodies in Schizophrenia.

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.

A study of type-1 diabetes associated autoantibodies in schizophrenia.

Epidemiological studies revealed an association between type-1 diabetes (T1D) and schizophrenia but the findings reported to date have been controversial. To clarify the inconsistency across studies, T1D-associated autoantibodies were examined in plasma samples collected from 272 patients with schizophrenia and 276 control subjects. An in-house enzyme-linked immunosorbent assay (ELISA) was developed using three linear peptide antigens, one of which was derived from glutamic acid decarboxylase (GAD) and two were derived from insulinoma-associated antigen 2 (IA2). Mann-Whitney U test showed a significant decrease in the levels of plasma IgG against the IA2b antigen in schizophrenia patients as compared to control subjects (Z=-3.54, p=0.0007), while no significant difference was found between these two groups either in anti-IA2a IgG levels (Z=-1.62, p=0.105) or in anti-GAD IgG levels (Z=-1.63, p=0.104). Linear regression analysis indicated no association of antipsychotic medication with the levels of plasma IgG against IA2a, IA2b or GAD, while the levels of plasma IgG for these 3 peptide antigens were significantly correlated with each other. Binary logistic regression showed that neither the DQ2.5 variant nor the DQ8 variant was associated with circulating levels of 3 T1D-associated autoantibodies in both the patient group and the control group. The coefficient of variation was 10.7% for anti-IA2a IgG assay, 10.1% for anti-IA2b IgG assay and 10.7% for anti-GAD IgG assay. The present work suggests that T1D-associated antibodies are unlikely to confer risk of schizophrenia and that the in-house ELISA developed with linear peptide antigens is highly reproducible.