Dominique Endres1, Katharina von Zedtwitz1, Isabelle Matteit1, Isabel Bünger2, Helle Foverskov-Rasmussen2, Kimon Runge1, Bernd Feige1, Andrea Schlump1, Simon Maier1, Kathrin Nickel1, Benjamin Berger3, Miriam A Schiele1, Janet L Cunningham4, Katharina Domschke5, Harald Prüss6, Ludger Tebartz van Elst7. 1. Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 2. Department of Neurology and Experimental Neurology, Universitätsmedizin Berlin, Berlin, Germany; German Center for Neurodegenerative Diseases Berlin, Berlin, Germany. 3. Clinic of Neurology and Neurophysiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 4. Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden. 5. Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Center for Basics in Neuromodulation, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 6. Department of Neurology and Experimental Neurology, Universitätsmedizin Berlin, Berlin, Germany; German Center for Neurodegenerative Diseases Berlin, Berlin, Germany. Electronic address: harald.pruess@charite.de. 7. Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. Electronic address: tebartzvanelst@uniklinik-freiburg.de.
Abstract
BACKGROUND: Autoimmune psychosis may be caused by well-characterized anti-neuronal autoantibodies, such as those against the NMDA 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 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 immunoglobulin G 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 = .026) and white matter changes (p = .020) more frequently than 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.
BACKGROUND: Autoimmune psychosis may be caused by well-characterized anti-neuronal autoantibodies, such as those against the NMDA 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 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 immunoglobulin G 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 = .026) and white matter changes (p = .020) more frequently than 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.
Authors: Dominique Endres; Luciana Hannibal; Benjamin Zaltenbach; Miriam A Schiele; Kimon Runge; Kathrin Nickel; Benjamin Berger; Katharina Domschke; Nils Venhoff; Harald Prüss; Ludger Tebartz van Elst Journal: Front Immunol Date: 2022-08-30 Impact factor: 8.786