004 – Antibody repertoire and antigen recognition of B lineage cells in a unique case of human autoimmune encephalitis
Manuela Paunovic (1) – Eduardo Beltran (2) – Emine Cesur (1) – Klaus Dornmair (2) – Monika Bradl (1) – Hans Lassmann (1)
Department of Neuroimmunology, Center for Brain Research, Medical University of Vienna, Austria (1) – Department of Clinical Neuroimmunology, Ludwig Maximilian University of Munich, Germany (2)
Autoimmune diseases affecting the central nervous system (CNS) have been observed after active sensitization with brain tissue or brain cells, leading among others also to acute encephalitis (AE), a disease which reflects inflammatory and demyelinating conditions similar to multiple sclerosis (MS). In this project, we analysed one archival autopsy tissue obtained from a patient who died after repeated exposure to subcutaneous injections of lyophilized brain cells. A detailed pathological examination in our laboratory revealed that this patient suffered from massive demyelination, as evidenced by the presence of large demyelinated perivenous areas and demyelinated periventricular lesions surrounded by activated macrophages containing myelin degradation products. This pattern of demyelination strongly mimicked the pathology of MS. We then further studied this case and found a high number of CD20 positive B lineage cells in the perivascular inflammatory infiltrates. Among this cell population, a high number of IgG or IgM and CD138 positive plasma cells were present. We are now interested in the following research question:
Which antibody repertoire is expressed by the B lineage cells in the human autoimmune encephalitis case described above?
In a first step to address this question, we isolated RNA from this tissue and performed next generation sequencing (NGS). We were able to identify clonal expansion of one heavy and one light chain. In a next step, we will test whether these chains can form a functional antibody, which is a prerequisite for further antigen searches.
This work is supported by the Austrian Science Funds (FWF, project I3335-B27).