The University of Oslo arranges digital public defences this semester, thus the disputation will be held as a video conference over Zoom.
The public defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.
Click here to participate in the public defence
Digital Trial Lecture – time and place
Adjudication committee
- First opponent: Associate professor Joachim Burman, Uppsala University Hospital
- Second opponent: Researcher Sonia Gavasso, Haukeland University Hospital
- Third member and chair of the evaluation committee: Associate Professor Shuo-Wang Qiao, University of Oslo
Chair of the Defence
Professor Ludvig Andre Munthe, University of Oslo
Principal Supervisor
Professor Trygve Holmøy, University of Oslo
Summary
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In multiple sclerosis, immune cells attack the central nervous system and are associated with areas of demyelination causing disability in patients. Interest in the pathological role of B cells has increased after the introduction of clinically effective B cell depleting therapies. Clonal expansion of T and B cells intrathecally suggests antigen specific responses are driving the inflammation, and collaboration between these cell types have been suggested to be dysregulated. Identifying the disease driving agent, cell or process is therefore a major goal. In this thesis, Rune A. Høglund discusses the potential of idiotopes as drivers of this T-B collaboration. Idiotopes are epitopes derived from immunoglobulin variable regions, and thus the B cell receptors themselves. It has previously been demonstrated that T cells specific to idiotopes can initiate and drive pathogenic immune responses. Due to the diversity of immunoglobulin repertoires, this has been a challenge to pursue in patient materials. By using neural network prediction tools, we were able to identify key areas in immunoglobulin variable regions with predicted high affinity for human leukocyte antigen class II molecules. These were associated with areas of high likelihood for endosomal processing. The prediction accuracy was validated using in vitro assays to identify key factors in immunoglobulin degradation and to identify autologous, idiotope-specific T cells. Our findings suggest that multiple sclerosis patients have a repertoire of idiotope-specific T cells, possibly participating in a dysregulated response, and indicate the prediction tools can help identify these. Additionally, we investigated the effects of the drug dimethyl fumarate on B cells, in a small cohort of patients. The thesis addresses how idiotope-driven T-B collaboration fits with current knowledge of multiple sclerosis immunopathology and our understanding of therapeutic mechanisms of action. |
Additional information
Contact the research support staff.