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


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Hoffmann C., Zong S., Mané-Damas M., Stevens J., Malyavantham K., Küçükali C. İ. , ...More

Schizophrenia Research, vol.228, pp.462-471, 2021 (Journal Indexed in SCI)

  • Publication Type: Article / Article
  • Volume: 228
  • Publication Date: 2021
  • Doi Number: 10.1016/j.schres.2020.12.038
  • Title of Journal : Schizophrenia Research
  • Page Numbers: pp.462-471

Abstract

The etiology of psychotic disorders is still unknown, but in a subgroup of patients symptoms might be caused by

an autoimmune reaction. In this study, we tested patterns of autoimmune reactivity against potentially novel

hippocampal antigens. Serum of a cohort of 621 individuals with psychotic disorders and 257 controls were

first tested for reactivity on neuropil of rat brain sections. Brain reactive sera (67 diseased, 27 healthy) were further

tested 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 prevalence

of 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 patterns

in both diseased and control groups. Upon screeningwith GAD CBA, one of these patternswas identified as

GAD65 in one individual with schizophrenia and also in one healthy individual. Two diseased and two healthy

individuals had low antibody levels targeting GAD67 by CBA. Antibody reactivity on HEp-2-substrate was increased

in patients with schizoaffective disorder, but only in 3 patients did antibody testing hint at a possible diagnosis

of systemic lupus erythematosus. Although reactivity of serum to intracellular antigens might be

increased in patients with psychotic disorder, no specific targets could be identified. GAD antibodies are very

rare and do not seem increased in serum of patients with psychotic disorders.