This PhD thesis focuses on improving treatments for rheumatoid arthritis (RA). In RA, the immune system inadvertently attacks healthy joints, causing pain and swelling. Specific B cells play a key role here: some become confused and recognise body substances, triggering an inflammatory response.
Current RA treatments suppress all B cells, which increases the risk of infection. Our research focused on methods to target only the confused B cells. We recreated a body substance called CCP4 in the lab, which was recognised only by the confused B cells. We then investigated how best to target and eliminate these B cells.
We found that combining two CCP4 molecules improved the recognition of confused B cells. However, adding a toxin to CCP4 to disable the B cells proved ineffective. In addition, we developed a mark-and-grab technique, which improved B-cell capture. Finally, we tested a super-activation technique that makes the B cells die by giving them lots of CCP4. In conclusion, in this PhD thesis, we explored various strategies to specifically knock out confused B cells. Further research in this field offers a promising prospect for new treatments in RA.
Margot van Weijsten was born in The Hague on 27 October 1994. She completed her pre-university education at the Stedelijk Gymnasium Leiden, after which she studied Science at Radboud University Nijmegen (biochemistry track). During her Master's, she did internships at ModiQuest (now Immunoprecise) in Oss and with the Ger Pruijn's Biomolecular Chemistry research group. After completing her studies, she started her PhD in chemical immunology with Dr Kim Bonger's group. In her research, she investigated multiple ways to selectively disable autoreactive B cells in rheumatoid arthritis. She is currently completing this research as a postdoc researcher.