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Huib de Jong

Thursday 10 January 2013

Epitope hunting in rheumatoid arthritis, towards antigen specific immunotherapy

Promotor: Prof.dr Prakken & Prof.dr. Bijlsma
Defence: 10 January 2013

In auto-immune diseases such as rheumatoid arthritis and sjogren’s syndrome tolerance mechanisms fail leading to chronic inflammation, tissue damage and finally clinical symptoms. Restoring this self-tolerance is the ultimate goal for the clinical rheumatologist. In most experimental models of autoimmunity, antigen specific immune therapy is an effective way to achieve this. To translate this into antigen specific tolerance induction in RA requires the identification of peptide epitopes of these antigens.

In this thesis we discuss the different strategies used to identify peptide epitopes (chapter 1) and present the identification of new HSP60 epitopes (chapter 2), new proteoglycan aggrecan epitopes (chapter 3) and new HSP70 epitopes (chapter 4) in RA and/or healthy controls. Interestingly the phenotype of the response induced was different, depending upon the epitope admitted. We also showed that this approach is not always successful. In pSS patients for example we were able to detect an HSP60 specific response but were unable to detect a HSP60 epitope specific response (chapter 6).

In conclusion the presented epitopes in this thesis are new targets for epitope specific immunotherapy in rheumatoid arthritis.