Title: Identifying the cellular and genetic profile of salivary gland damage in Sjogren’s Syndrome with focus on how specific tissues influence disease at single-cell level
Funder: The Academy of Medical Sciences

Abstract: Sjogren’s syndrome is a common cause of impaired production of saliva that leads to prolonged and irreversible dry mouth. The loss of salivary gland function leads to reduction or absence of saliva, which negatively impacts upon eating, speaking, swallowing and taste as well as lessening quality of sleep, increasing the risk of dental decay and periodontal disease, lessening wellbeing of affected individuals. There remains no means of halting progression or reversing the disease process, hence treatment is still directed towards replacement of saliva and prevention of complications. The aim of this study is therefore to map and understand the cell population heterogeneity of human salivary glands in Sjogren’s Syndrome (SS) that are influencing their progressive damage in relation to disease state. SS is an autoimmune disorder that ultimately destroys the acinar cells of the salivary and lacrimal glands, and possess limited regenerative capabilities. Despite the advent of novel treatments such as biological agents to regulate the immune system and stimulation of nerves, these are still not well tolerated and present important side effects. In order to create new research-based therapies, it is vital to understand SS further, and this study will utilise a cutting-edge technology of single-cell RNA sequencing. This allows the recognition of specific genetic changes in each cell population of the salivary glands in SS compared to healthy tissues. This would then enable the identification of novel markers and proposing new ways of targeting the disease to prevent further damage and loss of function.

Lay abstract: Prolonged dryness of the mouth can greatly lessen the wellbeing of affected individuals as it compromises speech, eating, swallowing, taste and the wearing of dentures, increases the risk of dental decay and gum disease and lessens quality of sleep. Sjogren’s syndrome (SS) is a common cause of irreversible dryness of the mouth and eyes. There is an attack by the body defence (immune) system upon the salivary and lacrimal (tear) glands that results in a partial or total loss of saliva and/or tears. It remains difficult to identify patients with early disease and there remains no way of halting or reversing the immune attack upon these glands. Of additional worry, about 5% of patients with SS will later develop cancer – non-Hodgkin’s lymphoma, which while having a good prognosis still requires patients to have complex cancer treatment. Custom-made treatments to regulate the immune system or body secretions have been utilised, however still not well accepted due to poor tolerance and side effects. A blood sample can show if specific immune cells are present, however it is unknown how and what other factors influence their accumulation around the salivary glands that leads to their damage and dry mouth. This raised the question: what changes in the salivary glands are influencing their progressive damage in Sjogren’s Syndrome? This study aims to use new technology to find very specific genetic changes in each compartment of salivary glands that can help understanding SS better and create new options of treatment based on scientific findings.

Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INFLAMMATORY AND IMMUNE SYSTEM