Einzelzell-basierte hoch auflösende Charakterisierung der intrathekalen Immunität bei der Autoimmun Encephalitis

In this proposal we aim to study the immune mechanisms, which systemically protect us from infections and cancer, but in the context of the central nervous system (CNS) can cause inflammation and auto-immunity against neurons and synapses. The disease condition is named autoimmune encephalitis (AIE) and – although rare – is increasingly being recognized. It can cause – among others – progressive memory loss, mood disturbances and seizures. We previously found a small number of markers that are predictive for the disease, but a full-scale unbiased characterization of autoimmunity in AIE has not been performed. Using advanced single cell technologies and analytics, we here propose to characterize the cell types, markers, pathways and genes that are specific to AIE with extremely high resolution and precision. We are a unique and focused group of clinicians and researchers treating and studying a large cohort of AIE patients and managing large biomaterial banks, which include sufficient patient material for our study. We have also developed and calibrated new genomic technologies to construct very detailed models of immune cells and pathways in autoimmune diseases. Our group thus combines cutting-edge technology with access to rare clinical specimen and a long-standing expertise in diagnosing this heterogeneous disorder. This will enable us to better understand how immune cells interact with the inflamed brain. This outstanding combination of world leading scientists and clinicians with new technologies makes us especially well equipped to break new grounds in AIE research. We propose that an ultra-high resolution phenotyping of local immune responses, using single cell genomic analysis of the CSF will provide a basis for better understanding, diagnosing, predicting and treating AIE in the future.