Restoring immune balance in patients with patients with primary Sjogrens Syndrome (pSS) by modulating microRNA expression

Sjogren's Syndrome (SS) is an autoimmune disease which affects 0.3-0.5% of people in the developed world. SS can occur at any age but is most common between the ages of 40 and 60. Women are 9 times more likely to suffer from SS than men. Specialised secretory glands that produce saliva, tears, and bowel secretions are targeted for destruction. As a result of this, these glands stop working leading to dry eyes, dry mouth, dry skin and also dryness of the large intestine. SS occurs when our immune system, which normally provides protection from infection, begins to attack parts of the body instead. The main cell types involved are specialised immune cells which under normal conditions provide protection from infection through the production of key soluble protein mediators which promote inflammation as well the production of antibodies.
There is currently no cure for SS and the exact cause is unknown, although genetic and environmental factors are thought to play a role. The body's response to both bacterial and viral infections is also thought to contribute to disease development and severity, via inappropriate activation of anti-viral innate immune receptors, Toll like Receptors (TLRs), TLR7 and TLR9, specifically. If these pathways are not properly regulated this could lead to the over production of key proteins which result in inflammation and eventually lead to secretory gland destruction. A new regulatory network controlled by short endogenous non-coding single-stranded RNA oligonucleotides termed microRNAs or miRs has been identified. These miRs bind to mRNA and repress or limit the production of inflammatory proteins. Given the potential importance of miR expression in controlling inflammation in SS patients, we propose to characterise miR expression in SS patients and establish if they are functioning inappropriately leading to the enhanced production of inflammatory cytokines which contributes to secretory gland destruction.

Award Date: 19 June 2014
Award Value: €39,490
Principal Investigator: Ms Emma-Jayne Verner
Host Institution: Royal Victoria Eye and Ear Hospital Research Foundation Ltd
Scheme: MRCG-HRB Joint Funding Scheme