Areas of investigation/research focus
An increasing number of neuropsychiatric diseases are caused by pathogenic anti-neuronal antibodies, ranging from acute encephalitis to slowly progressive dementia. Antibodies against the NMDA-type glutamate receptor are prototypical for this new disease group. Patients with IgG NMDA receptor autoantibodies develop a severe encephalitis with psychiatric features. In contrast, IgA antibodies are associated with progressive cognitive impairment.
Our research focuses on the detailed analysis of mechanisms of autoantibody-mediated impairment of neuronal function. For this, individual antibody-secreting cells from the cerebrospinal fluid of affected patients are isolated. Molecular biology techniques then allow the recombinant production of autoantibodies derived from these cells. This novel methodology could, for the first time, demonstrate that the antibodies are directly pathogenic, thus leading to synaptic changes in hippocampal neurons. We are currently expanding the technology to additional disease-related antibodies, such as against AMPA receptors, GABA receptors, glycine receptors, LGI1, GAD or IgLON5. The monoclonal human antibodies are ideal tools for high-resolution microscopy and targets for innovative immunotherapies in patients with psychosis or dementia.
Experimental results provide insight into the molecular cascades of neuronal damage, thus representing an important translational approach to identify patients that could benefit from immunotherapy.