impact of microbiota for induction of pathogenic, brain-specific antibodies

• Applicants: Dr. Andrey A. Kruglov; Professorin Dr. Britta Siegmund
• Subject Area: Molecular and Cellular Neurology and Neuropathology ; Immunology ; Clinical Immunology and Allergology ; Clinical Neurology; Neurosurgery and Neuroradiology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 504745852

There is increasing evidence for the role of microbiota for the development of central nervous system pathology, the so-called “gut-brain” axis. Our preliminary data further expand the understanding of this interplay by showing that autoantibodies binding CNS tissues may originate in lamina propria B cells, and that human monoclonal antibodies found in the cerebrospinal fluid (CSF) of patients with various CNS pathologies exhibit strong microbiota reactivity. Thus, the central question of our proposal is whether microbiota-directed antibodies may drive antibody-mediated neuropsychiatric diseases. A bidirectional strategy using human samples and mouse models, i.e., analysis of pathological properties in the CNS by antibodies derived from lamina propria and of microbiota binding by pathogenic antibodies cloned from neurological patients, will be implemented to address the “gut-brain” molecular mimicry on the molecular level. The research program will establish a link between CNS autoantibodies and microbiota and will be further utilized with several members of the consortium to elucidate the possible environmental, microbiota-derived triggers of CNS antibody-mediated neuropsychiatric diseases.

• DFG Programme: Clinical Research Units
• Subproject of: KFO 5023: BECAUSE-Y Berlin Center for Diagnosing, Understanding and Treating Antibody(Y)-mediated Neurological Diseases