| Description |
Primary Sjogren's syndrome (pSS) is an autoimmune disorder, predominantly affecting women, that causes dry eyes, dry mouth, fatigue, and other extraglandular manifestations (Le Goff et al., 2017). It has been shown that chronic pathogen exposure can lead to development of autoimmune diseases such as Sjogren's syndrome (Bjork et al., 2020; Ram et al., 2008). In a previous study, Hepatitis Delta Virus (HDV) antigen and sequence were detected in pSS minor salivary gland (MSG) tissue, and expression of HDV antigens in murine salivary gland reproduced the complete pSS phenotype (Weller et al., 2016). HDV is a single stranded satellite RNA (satRNA) virus with a circular genome containing only one open reading frame encoding the small delta antigen (S-HDAg) and large delta antigen (L-HDAg) (Taylor, 2020; Alves et al., 2013). S-HDAg initiates replication once intracellular, whereas L-HDAg assembles virions (Lai, 1995). Building upon the initial discovery of HDV in pSS, this study was designed to further evaluate HDV profiles in an Utahn pSS patient cohort. In situ hybridization and immunohistochemical techniques were utilized to detect HDV sequence and HDAg in pSS minor salivary gland tissue, respectively. RNAscope® was utilized to detect HDV genomic and anti-genomic RNA. Immunohistochemical detection of HDAg, cellular markers and mitochondrial proteins was used to detect cellular and subcellular localization of HDAg. HDV genomic RNA was detected and found to co-localize with nuclei of salivary gland cells. HDAg was present at varying levels of intensity in salivary gland cells and co-localizing with both nucleus and mitochondria. iii Currently, the etiology of Sjogren's syndrome is not well defined. Due to this, available therapies to treat pSS are limited to lubricants for the eyes and mouth, immunosuppressives, diet alterations, smoking cessation, and other therapeutics to improve quality of life (Fox et al., 2021). Understanding where and how HDV interacts within the salivary gland tissue is essential for the development of targeted therapeutics to treat and/or cure Sjogren's syndrome. |
