Plasma autoreactivity was assessed in the following three actions: first, we screened for antibody reactivity toward 2304 protein fragments, representing 1812 human protein-coding genes, by using planar protein microarrays. patients were diagnosed with schizophrenia, delusional disorder, schizoaffective disorder, bipolar disorder or a long-term unspecified nonorganic psychosis during follow-up, whereas 23 patients achieved complete remission. At the end of follow-up, plasma samples were analyzed for IgG reactivity to 2304 fragments of human proteins using a multiplexed affinity proteomic technique. Eight patient samples showed autoreactivity to the N-terminal fragment of the PAGE (P antigen) protein family (PAGE2B/PAGE2/PAGE5), whereas no such autoreactivity was seen among the controls. PAGE autoreactivity was associated with a significantly increased risk of being diagnosed with schizophrenia during follow-up (odds ratio 6.7, relative risk 4.6). An immunohistochemistry analysis using antisera Tacrolimus monohydrate raised against the N-terminal fragment stained an unknown extracellular target in human cortical brain tissue. Our findings suggest that autoreactivity to the N-terminal portion of the PAGE protein family is associated with schizophrenia in a subset of patients with first-episode psychosis. Introduction Psychiatric diagnostics is based almost exclusively on observed behavioral characteristics and self-reporting, with few existing biological correlates that are clinically useful.1 The lack of refined diagnostic tools makes it difficult to distinguish clinically relevant subgroups of psychiatric disorders, although such stratification would possibly improve treatment outcomes. In the case of schizophrenia, it is well established that aberrations in the dopamine system play an important role in the pathogenesis, in addition to a strong underlying genetic component, and stress.2 Further, a growing body of literature suggests that immunology has a role in the development of the disease, at least in a subgroup of patients.3 Some autoimmune diseases, including diabetes mellitus type 1, Graves disease and systemic lupus erythematosus, are more prevalent in patients with schizophrenia compared with the general population.4 Others, such as rheumatoid arthritis, are rarer than would be expected.5 In addition, both positive and negative associations between human leukocyte antigen polymorphisms and schizophrenia have been reported.3, 6, 7 To our knowledge, the first article on autoantibodies in patients with schizophrenia was published in 1937.8 Since then, many studies have investigated autoreactivity and its possible association with psychosis. In conclusion, a majority of these studies show higher frequencies of autoantibodies in psychotic patients compared with controls.7 Specifically, autoantibodies in serum directed to the N-methyl-D-aspartate receptor and the voltage-gated potassium channel have been reported in patients with first-episode psychosis.9 However, a recent review article concluded that autoantibodies towards brain antigens may be equally prevalent in healthy controls.10 Hence, it remains unclear whether autoimmunity has an etiopathological role in psychosis, and, if so, in all cases or in a subgroup of patients. In this study, we utilized a unique collection of thousands of protein fragments generated within the Human Protein Atlas (www.proteinatlas.org), Tacrolimus monohydrate together with protein microarrays, to search for autoantibody reactivity in plasma samples. Analyzing 53 patients with first-episode psychosis and 41 non-psychotic controls, our aims were to explore the association between autoantibodies and psychosis Tacrolimus monohydrate and to study whether any certain autoantibody reactivity was associated with the Rabbit polyclonal to NR4A1 severity of psychotic symptoms and/or the eventual establishment of any DSM-IV-defined disorder characterized by chronic or relapsing psychotic symptoms. We hypothesized that a subgroup of patients would have a higher level of autoreactivity compared with the nonpsychotic controls, and that pronounced autoreactivity would be associated with increased symptom severity and chronification. Materials and methods Experimental study design The study was carried out in four actions. First, we performed a cross-sectional study analyzing plasma samples from 53 patients with first-episode psychosis and 41 controls, assessing differences in autoimmune reactivity by using an untargeted protein microarray set-up, and secondly, confirming the results with a full-length protein in an enzyme-linked immunosorbent assay (ELISA) analysis. Thirdly, we conducted a clinical follow-up study including all 53 patients, investigating whether autoimmune Tacrolimus monohydrate reactivity at admission was associated with symptom severity or could predict subsequent development of schizophrenia, delusional disorder, schizoaffective disorder, bipolar disorder or long-term unspecified nonorganic psychosis. Fourthly, we performed a complementary immunohistochemistry analysis using.