The search for an autoimmune origin of psychotic disorders: Prevalence of autoantibodies against hippocampus antigens, glutamic acid decarboxylase and nuclear antigens

Abstract

The etiology of psychotic disorders is still unknown, but in a subgroup of patients symptoms might be caused byan autoimmune reaction. In this study, we tested patterns of autoimmune reactivity against potentially novelhippocampal antigens. Serum of a cohort of 621 individuals with psychotic disorders and 257 controls werefirst tested for reactivity on neuropil of rat brain sections. Brain reactive sera (67 diseased, 27 healthy) were furthertested for antibody binding to glutamic acid decarboxylase (GAD) isotype 65 and 67 by cell-based assay(CBA). A sub-cohort of 199 individuals with psychotic disorders and 152 controls was tested for the prevalenceof anti-nuclear antibodies (ANA) on HEp2-substrate aswell as for reactivity to double-strandedDNA, ribosomal P(RPP), and cardiolipin (CL). Incubation of rat brainwith serumresulted in unidentified hippocampal binding patternsin both diseased and control groups. Upon screeningwith GAD CBA, one of these patternswas identified asGAD65 in one individual with schizophrenia and also in one healthy individual. Two diseased and two healthyindividuals had low antibody levels targeting GAD67 by CBA. Antibody reactivity on HEp-2-substrate was increasedin patients with schizoaffective disorder, but only in 3 patients did antibody testing hint at a possible diagnosisof systemic lupus erythematosus. Although reactivity of serum to intracellular antigens might beincreased in patients with psychotic disorder, no specific targets could be identified. GAD antibodies are veryrare and do not seem increased in serum of patients with psychotic disorders.