LAUSR

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.