Using a mouse model that naturally develops autoimmune Sjögren syndrome, the laboratory of Dr. Michael Dosch, an HSC senior scientist, has identified a protein (ICA69) that is a major target in the autoimmune response that results in Sjögren syndrome. They have also developed a prototype vaccine to treat this condition, which dramatically reduced the progression of tissue damage even relatively late in the disease in the animal model.
Sjögren syndrome is an autoimmune disease in which the body's immune system mistakenly attacks its own moisture producing glands - for example, the salivary (mouth) and lacrimal (tear duct) glands. Sjögren syndrome affects approximately one per cent of the population. Nine out of ten patients are women and the average age of onset is in the late 40s. About 50 per cent of the time Sjögren syndrome occurs alone, and 50 per cent of the time it occurs in the presence of another connective tissue disease. The four most common diagnoses that co-exsist with Sjögren syndrome are rheumatoid arthritis, systemic lupus, systemic sclerosis (scleroderma) and polymyositis/dermatomyositis.
The primary symptoms of Sjögren syndrome are dry eyes and dry mouth. It may also cause dryness of other organs, affecting the kidneys, gastrointestinal tract, blood vessels, lung, liver, pancreas, and the central nervous system. Many patients experience debilitating fatigue and joint pain. Symptoms can plateau, worsen, or go into remission. While some people experience mild symptoms, others suffer debilitating symptoms that greatly impair their quality of life. There is currently no effective therapy for Sjögren syndrome.
By removing the gene that produces the ICA69 protein, mice that normally develop Sjögren syndrome had no tear gland disease and a much reduced salival disease. In the mouse model, the prototype vaccine was able to stop disease progression.
"Our vaccine was able to stop Sjögren syndrome even after the disease had fully developed, an unusual finding, since in other autoimmune disorders it is impossible so far to stop and reverse the disease process once it is fully established," said Dr. Dosch, the study's principal investigator and a professor of Paediatrics and Immunology at U of T. "This finding is also exciting because it opens the door to further knowledge about treating selective organ autoimmune diseases, including the possibility of vaccines. In autoimmune diseases such as type 1 diabetes, it is difficult to assess the effectiveness and learn how to use vaccines, since the target organ cannot be examined. With Sjögren syndrome, the organ attacked by autoimmunity (the exocrine glands) are accessible to study, unlike the pancreas in diabetes, for example."
Dr. Dosch's research group collaborated with Dr. Arthur Bookman, a rheumatologist at Toronto Western Hospital, to compare the autoimmune response to the ICA69 protein in the mouse model to human patients, which was strikingly similar.
"We are planning a study that will involve at least 100 Sjögren patients so we can learn more about the connection between this protein and patients' autoimmunity in preparation for possible trials of the vaccine in humans," said Dr. Arthur Bookman, a co-author of the study, coordinator of the Multicisciplinary Sjögren's Clinic at the University Health Network, and an associate professor of Medicine at U of T.
Other collaborators on this research were: Shawn Winer (lead author), Igor Astsaturov, Roy Cheung, Hubert Tsui, Aihua Song, Roger Gaedigk, Daniel Winer, Anastasia Sampson, and Colin McKerlie, all from the HSC Research Institute.
This research was supported by the Canadian Institutes of Health Research, the Juvenile Diabetes Research Foundation, and The Hospital for Sick Children Foundation.
Additional Contact Information:
Jennifer Kohm, Public Affairs
Toronto Western Hospital
416-603-5323
jennifer.kohn@uhn.on.ca
Journal
The Lancet