Immunogenetic and immunological aspects of rheumatoid arthritis : DERAA and anti-citrulline reactivity can make the difference

Feitsma, A.L. (2010)

Doctoral Thesis

Rheumatoid arthritis (RA) is a chronic inflammation of several joints caused by autoimmunity. HLA molecules are most important risk factor involved in RA development. Regarding the risk of RA development, three variants can be discriminated; the shared epitope increases the risk, DERAA-containing HLA molecules decrease the risk and a neutral variant. In this thesis we describe that a mother, in contrast to a father, with a DERAA-containing HLA-molecule confers a life-long protection to her child against RA development with and without passing the gene responsible for the HLA-molecule. Furthermore, we describe that the T cells of HLA-DR4 positive RA patients can react against certain peptides derived from the citrullinated (a post-translational modification) vimentin protein in a citrulline-specific manner. Next to HLA-molecules there are several other genetic factors involved in the risk of RA development, e.g. PTPN22 and CD40. For the PTPN22 SNP associated with RA development, we showed that information on the presence of the PTPN22 SNP next to the presence of ACPA (antibodies specific for RA patients) does not give additive value to the prediction of RA development. On the contrary, the SNP has an influence on the level of ACPA present in the patient. For a SNP in the CD40 gene, we showed that it influences the severity and progression of RA.

• ACPA
• Citrullination
• HLA-DRB1
• DERAA
• Shared epitope
• PTPN22
• CD40
• SNP
• Rheumatoid arthritis

• All authors: Feitsma, A.L.
• Supervisor: Huizinga, T.W.J.; Vries, R.R.P. de
• Co-supervisor: Toes, R.E.M.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden University Medical Center (LUMC), Leiden University
• Date: 2010-02-11
• ISBN (print): 9789064643798
• Sponsorship: Abbott BV and Novartis