Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Microbiology and Immunology

Supervisor

Ewa Cairns

Abstract

Anti-citrulline immune responses contribute to rheumatoid arthritis (RA) development, and are linked with the expression of HLA-DR molecules that encode the Shared Epitope (SE). Immune responses to homocitrulline, a structural analog of citrulline, have been recently detected in RA, but their role in RA is unknown.

The objectives of this study were to examine the specificity of anti-homocitrulline antibodies for RA, the dependence of anti-homocitrulline responses on SE-expression, and the cross-reactivity of responses to homocitrulline and citrulline. These objectives were addressed in RA patients and in SE-expressing DR4tg mice using homocitrulline- and citrulline-rich peptides.

Anti-homocitrulline antibodies occurred specifically in RA. The SE was associated with the development of immune responses to homocitrulline and cross-reactivity to citrulline in homocitrullinated peptide-immunized mice. Anti-homocitrulline and anti-citrulline antibodies were cross-reactive in RA patients and DR4tg mice, and the responses to homocitrulline- and citrulline-containing peptides were immunologically related.

Available for download on Sunday, September 01, 2019


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