Authors: Alexander Romano, Matthew Hesterman, Rachel Hill, Melodie Weller
Mentors: Melodie Weller
Insitution: University of Utah
Sjogren’s Disease (SjD) is an autoimmune disease diagnosed by symptoms of reduced tear and saliva excretion, accumulation of lymphocyte foci in the salivary glands, and the occurrence of antibodies against Ro (SSA), La (SSB), and nuclear proteins. The cause of SjD is unknown, though previous studies have detected the sequence and antigens of Hepatitis Delta Virus (HDV) in the minor salivary gland acinar, ductal, and adipose cells of patients with SjD; without the typical presence of a Hepatitis B coinfection. In this study, murine models were transduced with Adeno-associated virus containing expression cassettes for Luciferase (control), small, large, or a combination of both small and large HDV antigens to evaluate the impact of HDV antigen expression on salivary gland function and SjD autoimmune disease development. After a ten- or four-month period, the models were analyzed. Findings included a significant increase of inflammation for samples expressing both small and large HDV antigens, a significant increase of anti-SSA(La) antibodies in samples expressing the short HDV antigen, and a correlation between increased overall inflammation and decreased overall saliva flow. Performing qPCR methods verified the amount of HDV in the submandibular glands and Illumina sequencing portrayed an increase in glycolysis and beta oxidation metabolism in models with detectible HDV sequence. The models showed significantly increased IgM expression in the HDV exposed murine models, without significant change of other antibodies. Future plans include an ELISA diagnostic assay to verify the antibody levels and further sequencing analysis. With this information we can build a better picture of the direct mechanisms of HDV-mediated changes in salivary gland dysfunction and determine the extent that HDV can inducing systemic SjD symptoms.