Basic disease mechanisms in rheumatoid arthritis

Scherer, H.U. (2013)

Doctoral Thesis

Rheumatoid Arthritis (RA) is a chronic inflammatory disorder that typically affects cartilage and bone of small and middle-sized joints. Infiltration of the synovium by inflammatory cells causes destruction of cartilage, erosion of the adjacent bone and ultimately loss of function of the affected joint. Systemic inflammation, often going in parallel, can affect several organs and has long-term impact on organ function. This thesis presents work that investigates several aspects of basic immunological disease mechanisms with relevance to the inflammatory immune response in RA. Specifically, three main research questions triggered the experiments presented and form the outline of this thesis: 1. Do regulatory T cells feature anti-inflammatory properties besides the inhibition of effector T cells, which could help explain their therapeutic effectiveness in a murine model of established arthritis? 2. Are there specific features of the immune response to citrullinated antigens that could contribute to inflammation in RA, and can analysis of these features help in understanding the characteristics of anti citrullinated protein antibody producing B cells and their development? 3. Do certain genetic variants that associate with RA susceptibility contribute also to disease progression, as evidenced by the rate of joint destruction in RA?

• Single nucleotide polymorphisms
• Rheumatoid arthritis
• Regulatory T cells
• Fc glycosylation
• Anti citrullinated protein antibodies
• Avidity

• All authors: Scherer, H.U.
• Supervisor: Huizinga, T.W.J.; Toes, R.E.M.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden University Medical Center (LUMC), Leiden University
• Date: 2013-04-25
• ISBN (print): 9789461693754
• Sponsorship: Dutch Arthritis Foundation (het Reumafonds), UCB, Roche, Thermo Fisher Scientific, MSD, AbbVie, Euro Diag- nostica, Teva, Pfizer.