Dissertation
Mast cell-mediated immune modulation in experimental Rheumatoid Arthritis and Atherosclerosis
In this research project, we aimed to obtain more insight in the role of mast cells in the immune driven disorders rheumatoid arthritis and atherosclerosis.
- Author
- D. van der Velden
- Date
- 29 September 2016
- Links
- Thesis in Leiden Repository
Rheumatoid arthritis and atherosclerosis are disorders affecting a large proportion of the world population. Although not completely understood, it is well accepted that the immune system plays a dominant role in the pathology and etiology of both diseases.
Mast cells, which are potent immune effector cells, are one the first immune cells that respond to invading pathogens by the release of preformed mediators. Mast cells can also be found around blood vessels and in the joint in the synovial layer. Here, mast cells can influence the micro-environment by the release of immune regulatory mediators that influence other local (immune) cells. In this research project, we aimed to obtain more insight in the role of mast cells in the immune driven disorders rheumatoid arthritis and atherosclerosis. Mast cells were found to modulate the early immune response in experimental arthritis and that the role of mast cells is limited once the clinical symptoms of arthritis have manifested. In a high number of RA patients, anti-citrullinated protein antibodies (ACPAs) can be detected and serve as a biomarker for a more progressive RA phenotype compared to seronegative RA patients, and we have now established that the presence of ACPA in non-RA cardiovascular patients may be of predictive value for future cardiovascular events as well. Furthermore, we show that mast cells contribute to the initiation and progression of atherosclerosis.
In conclusion, the research performed in this thesis shows that mast cells have immune modulating functions in models of immune driven disorders and future research will establish whether mast cell stabilization in auto-immune diseases is of therapeutic interest.