Spectrum of novel anti-CNS autoantibodies in the cerebrospinal fluid of 119 patients with schizophreniform and affective disorders

ABSTRACT

Background

Autoimmune psychosis may be caused by well-characterized anti-neuronal autoantibodies, such as against the N-methyl-D-aspartate receptor. However, the presence of additional anti-central nervous system (CNS) autoantibodies in these patients has not been systematically assessed.

Methods

Serum and cerebrospinal fluid (CSF) from patients with schizophreniform and affective syndromes were analyzed for immunoglobulin G (IgG) anti-CNS autoantibodies using tissue-based assays with indirect immunofluorescence on unfixed murine brain tissue as part of an extended routine clinical practice. After an initial assessment of patients with red flags for autoimmune psychosis (N=30), tissue-based testing was extended to a routine procedure (N=89).

Results

Based on the findings from all 119 patients, anti-CNS IgG autoantibodies against brain tissue were detected in 18% (N=22) of patients (serum 9%, CSF 18%) following five principal patterns: 1) against vascular structures, most likely endothelial cells (serum 3%, CSF 8%); 2) against granule cells in the cerebellum and/or hippocampus (serum 4%, CSF 6%); 3) against myelinated fibers (serum 2%, CSF 2%); 4) against cerebellar Purkinje cells (serum 0%, CSF 2%); and 5) against astrocytes (serum 1%, CSF 1%). The patients with novel anti-CNS autoantibodies showed increased albumin quotients (p=0.026) and white matter changes (p=0.020) more frequent compared to those who tested negative for autoantibodies.

Conclusions

The study demonstrates five novel autoantibody-binding patterns on brain tissue of patients with schizophreniform and affective syndromes. CSF yielded positive findings more frequently than serum analysis. The frequency and spectrum of autoantibodies in these patient groups may be broader than previously thought.