Monoclonal human auto-antibodies: novel tools for the understanding and treatment of neuropsychiatric symptoms

Abstract

The various clinical manifestations of autoimmune encephalitis made this disease group an exciting new field in Neurology and Psychiatry. Identification of numerous pathogenic auto-antibodies against neuronal tissue resulted in unprecedented diagnostic and therapeutic opportunities. This has led to a critical reappraisal also of symptoms in patients with psychosis and dementia, and in some instances resulted in re-classification of disease.We now increasingly generate patient-derived monoclonal auto-antibodies against neuronal surface proteins and demonstrate their direct pathogenicity to cause neuropsychiatric symptoms. This has two essential implications: First, patients with these types of pathogenic auto-antibodies harbour a clear risk factor for the development of psychiatric abnormalities. Second, given their pathogenicity, the primary goal of treatment must be the removal of auto-antibodies using state-of-the-art immunotherapy rather than symptomatic treatment including neuroleptics.The technological achievement of recombinant generation of disease-causing human auto-antibodies will allow in the future i) to clarify the specific role of a given auto-antibody for the disease mechanisms, including down-regulation of synaptic proteins; ii) to identify novel antibodies targeting yet unknown epitopes on neuronal or glial surfaces; iii) to develop novel antibody-specific treatments, such as CAAR T cells; and iv) to provide molecular tools for improved research into neuropsychiatric autoimmunity by using these human antibodies for high-resolution molecular imaging and animal models.Findings from these studies will likely change the current diagnostic concepts in patients with impairment of memory, cognition, affect and mood. It has become clear that the perpetual discovery of novel antibodies will continue and ultimately result in a better understanding of pathomechanisms and therapies in some forms of dementia and psychosis. Molecular research will be essential in Psychiatry in order to not overlook such treatable aetiologies as primary neurodegenerative or psychiatric disorders.