Role of autoantibodies for long-term outcome and cognitive function following ischemic stroke

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Autoantibodies are frequently detected in patients with ischemic stroke, however, their (patho)physiological role remains elusive. In experimental stroke B cells infiltrate the ischemic brain tissue in a delayed manner and form ectopic lymphoid structures (ELS). Post–stroke cognitive decline was associated with the occurrence of brain-infiltrating B cells and CNS antigen-specific antibodies in stroke patients. Cognitive decline was prevented by blocking ELS formation in a stroke model of mice, which strongly suggests a pathophysiological role of CNS -directed humoral immune responses. Here, we test the hypothesis that several of these autoantibodies contribute to long-term stroke outcome and to cognitive decline in mice and humans. To do so, we will exploit several established prospective stroke cohorts at the Charité, which we will systematically screen for pathogenic autoantibodies targeting CNS antigens, establishing clinical correlations with outcome parameters. In addition, we will clone and generate recombinant antibodies from ELS -derived plasma cells after murine stroke as well as from plasma cells obtained from cerebrospinal fluid (CSF) of stroke patients suffering from post-stroke cognitive decline. Functional effects of cloned antibodies will be assessed in mouse models of stroke and in cell culture models with partners of the consortium.