University of Western Ontario - Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Microbiology and Immunology

Supervisor

Dr. Ewa Cairns

Abstract

Rheumatoid Arthritis (RA) is an inflammatory autoimmune disease which causes joint destruction. RA pathogenesis involves citrullinated peptides binding to the shared epitope (SE) during autoantigen presentation, and subsequent Anti-Citrulline Antibody (ACA) production. Their target, citrulline, is very similar to homocitrulline.

The main objective of this study was to investigate anti-homocitrulline immune responses in RA. Specifically, it investigated if: i) Anti-Homocitrulline Antibodies (AHA) were RA specific by screening patients with various inflammatory rheumatic diseases and healthy individuals. ii) ACA also bound homocitrulline by affinity purification and characterization. iii) anti-homocitrulline immune responses involved the SE by computer modelling and immunization of mice.

Results showed that AHA were common in RA only, some ACA also bound homocitrulline, and the SE could accommodate homocitrulline but did not restrict anti-homocitrulline responses in mice. In conclusion, AHA are specific to RA and some ACA cross-react with homocitrullinated targets. The SE is not essential for anti-homocitrulline responses.