- Non-canonical NF-κB signaling in rheumatoid arthritis and beyond
- Award date
- 23 October 2015
- Number of pages
- Document type
- PhD thesis
- Faculty of Medicine (AMC-UvA)
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, affecting the synovial joints.
During the last 20 years the treatment of RA has markedly improved. Patients are nowadays not only treated with conventional disease-modifying antirheumatic drugs (DMARDs), but also with targeted therapies such as biologics that either target the effect of a specific cytokine (tumor necrosis factor (TNF)-blockers and antiIL-6-receptor antibody treatment), block immune cell interaction (CTLA4-Ig) or deplete a specific subset of immune cells (anti-CD20 B cell therapy), or a small molecule Jak inhibitor.
Histopathological research using synovial biopsies of RA patients has been valuable for expanding the knowledge about the pathogenesis of the disease and may be used to discover new therapeutic targets as well as to evaluate the effects of novel treatments. Synovial tissue analysis revealed that in RA many signal transduction pathways are activated. One of the most important ones is the nuclear factor-κB (NF-κB) pathway. In this thesis we investigate the role of the alternative or non-canonical NF-κB pathway in RA synovial inflammation with a strong focus on:
1. The role of this pathway in EC biology and angiogenesis, primarily in the context of RA and other types of synovial inflammation, as well as in tumor-associated angiogenesis;
2. The contribution of non-canonical NF-κB signaling to ectopic lymphoid neogenesis in synovial inflammation;
3. The importance of the non-canonical NF-κB pathway in immunoregulatory processes, including (extrathymic) AIRE expression.
- Research conducted at: Universiteit van Amsterdam
Thesis (complete) (Embargo until 23 October 2017)
Chapter 6: Extrathymic Autoimmune Regulator (AIRE) in rheumatoid arthritis synovial inflammation and the contribution of non-canonical NF-κB signaling to (extra)thymic AIRE (Embargo until 23 October 2017)
Chapter 7: General discussion & summary (Embargo until 23 October 2017)
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