Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Master of Science

Program

Microbiology and Immunology

Supervisor

Barra, Lillian

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes joint pain and damage. Studies have shown that inducing immune tolerance towards RA-specific proteins/peptides in RA mouse models can reduce arthritis severity and pro-inflammatory responses. The objectives of this study were to determine if a novel peptide cream treatment could modify RA-specific immune responses and reduce joint swelling in a humanized mouse model expressing the HLA-DRB1*0401 allele (known as DR4tg mice), the strongest genetic risk-factor for RA. Hyaluronan-Phosphatidylethanolamine cream infused with synthetic peptides HomoCitJED and CitJED was applied to HomoCitJED-immunized DR4tg mice before or after arthritis induction. Knee joint swelling and T cell and B cell responses to HomoCitJED and CitJED were measured in this study, however there were no significant differences between peptide-infused cream treated mice and controls. Further optimization of the peptide-infused cream is required to successfully modify immune responses and treat arthritis in DR4tg mice.

Summary for Lay Audience

Rheumatoid arthritis (RA) is a life-long autoimmune disease that causes joint swelling, damage and pain, affecting about 1% of the Canadian population. Current treatments for RA involve the use of drugs that do not stop the disease from developing. Instead, these treatments slow down the progression of RA by blocking basic immune responses, and only alleviate some of the pain and symptoms. Additionally, these treatments have severe side effects. Thus, there is a need for a new treatment that is able to treat RA without blocking immune function. In RA, abnormal immune responses to proteins, or small pieces of proteins called citrullinated and/or homocitrullinated peptides, have been shown to be involved in the development of the disease. The development of RA is also associated with the expression of the strongest genetic risk factor for RA called the Shared Epitope. We have previously shown that mice containing the Shared Epitope develop immune responses seen in RA patients when injected with homocitrullinated peptides. We believe that applying citrullinated and homocitrullinated peptides onto the skin of these mice using a new cream might be able to modify immune responses and treat RA. In this study, the cream was applied to mice that contain the Shared Epitope either before or after arthritis onset. We found that the application of this cream did not modify immune responses or reduce joint swelling in mice that received the cream treatment. Therefore, this new cream treatment requires adjustments in order for it to effectively treat RA.

Available for download on Thursday, June 01, 2023

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