Autoantibody profiles associated with clinical features in psychotic disorders

Abstract

Autoimmune processes are suspected to play a role in the pathophysiology of psychotic disorders. Better understanding of the associations between auto-immunoglobulin G (IgG) repertoires and clinical features of mental illness could yield novel models of the pathophysiology of psychosis, and markers for biological patient stratification. We undertook cross-sectional detection and quantification of auto-IgGs in peripheral blood plasma of 461 people (39% females) with established psychotic disorder diagnoses. Broad screening of 24 individuals was carried out on group level in eight clinically defined groups using planar protein microarrays containing 42,100 human antigens representing 18,914 proteins. Autoantibodies indicated by broad screening and in the previous literature were measured using a 380-plex bead-based array for autoantibody profiling of all 461 individuals. Associations between autoantibody profiles and dichotomized clinical characteristics were assessed using a stepwise selection procedure. Broad screening and follow-up targeted analyses revealed highly individual autoantibody profiles. Females, and people with family histories of obesity or of psychiatric disorders other than schizophrenia had the highest overall autoantibody counts. People who had experienced subjective thought disorder and/or were treated with clozapine (trend) had the lowest overall counts. Furthermore, six autoantibodies were associated with specific psychopathology symptoms: anti-AP3B2 (persecutory delusions), anti-TDO2 (hallucinations), anti-CRYGN (initial insomnia); anti-APMAP (poor appetite), anti-OLFM1 (above-median cognitive function), and anti-WHAMMP3 (anhedonia and dysphoria). Future studies should clarify whether there are causal biological relationships, and whether autoantibodies could be used as clinical markers to inform diagnostic patient stratification and choice of treatment.

Biomarkers of neurodegeneration in neural autoantibody-associated psychiatric syndromes: A retrospective cohort study

“…Our studies show that many different autoantibodies are associated with psychiatric syndromes that in turn can reveal various symptoms, courses, and possibly prognoses. These observations are consistent with other studies' [ [20] , [21] , [22] , [23] ]. In addition, there appears to be no significant neurodegeneration difference between psychiatric syndromes with and without autoantibodies.…”

Autoantibodies against Central Nervous System Antigens and the Serum Levels of IL-32 in Patients with Schizophrenia

“…The presence of autoantibodies in schizophrenia can indicate a dysfunction of the immune system, which may play a role in the pathogenesis of the disease in some cases and may not play any role in the pathogenesis of the disease in other cases. Collectively, various studies suggest that more extensive evaluation is needed to prove that immune system dysfunction may play a role in the pathogenesis of schizophrenia [42] Some limitations of this study include the low number of patients and the serum levels of autoantibodies in this study. Therefore, we suggest that the serum levels of autoantibodies may be determined in CSF.…”

Development of a protein microarray for profiling circulating autoantibodies in human diseases

“…Production of AAbs can be accompanied by disease progression, such as autoimmune diseases, cancer, diabetes, and cardiovascular disease [1–4]. As such, AAbs have great value in understanding autoimmunity as well as clinical applications [5–9].…”