Applied and Translational Research Program
Center for Biotechnology and Innovation
Objective: The purpose of this initiative is to stimulate research to elucidate the mechanisms underlying the pathogenesis of Sjögren’s syndrome. In the context of this initiative, integrative, multidisciplinary research approaches will be encouraged.
Background: Sjögren’s syndrome is a systemic autoimmune disease affecting 1 million or more Americans. Primary Sjögren’s syndrome occurs alone while secondary Sjögren’s syndrome presents in connection with other autoimmune diseases such as rheumatoid arthritis or systemic lupus erythematosus. Sjögren’s syndrome disproportionally affects women, at a ratio of 9:1 over men and is typically diagnosed in the 5th or 6th decade of life. Diagnostic criteria include lymphocytic infiltration of salivary glands, dry mouth, dry eyes and circulating autoantibodies to Ro/SS-A and La/SS-B antigens. The disease results in irreversible salivary gland tissue damage and loss of saliva. Without the lubricating and protecting function of saliva the oral cavity is highly susceptible to infections, including rampant caries and candidiasis, dysphagia, oral pain and discomfort. The sequelae of dry mouth result in significantly reduced quality of life for the patients.
Sjögren’s syndrome is a complex disease that involves interplay of genetic and environmental factors. To date few of these factors are well understood. As a result, there is a lack of diagnostic markers and diagnosis usually lags onset by 6-10 years. Since no effective therapy is available, current patient management typically consists only of palliative treatment. To develop preventive measures and therapies for Sjögren’s syndrome, the gaps in scientific and clinical knowledge must be addressed and a more precise molecular understanding of the pathophysiology of Sjögren’s syndrome must be developed. The following are examples of potential research areas:
1. Identification of human genetic risk factors for Sjögren’s syndrome.
2. Development and validation of new animal models.
3. Identification of the critical triggers, environmental factors and molecular pathways underlying the disease
4. Delineation of the immunological aspects of Sjögren’s syndrome
5. Identification of biomarkers for early diagnosis, determination of disease progression, glandular dysfunction and stratification of high risk individuals;
6. Elucidation of clinically relevant outcome measures for trial of new therapeutics, including measures of oral, ocular and systemic manifestations of the disorder.
The initiative is timely for the following reasons:
- The NIDCR supported International Sjögren’s Syndrome Registry, currently active and productive, allows access to well characterized biological specimens
- Sjögren’s syndrome stands to benefit from unprecedented advances in genomics, transgenic biology, proteomics, autoimmunity and immunobiology.
Current Portfolio Overview: Intramural NIDCR has an existing, well-recognized leadership position in Sjögren’s syndrome and the Institute has the primary responsibility for addressing oral diseases at the NIH campus. Moreover, the NIDCR Extramural program supports almost one half of the currently NIH funded awards for Sjögren’s syndrome (13 of 30 awards). These awards mainly include studies on: i) the immunological and inflammatory mechanisms of Sjögren’s syndrome; ii) the role of apoptosis in salivary gland destruction; iii) mapping and identification of candidate genes associated with Sjögren’s syndrome; and iv) the basic mechanisms of salivary gland fluid secretion in health and disease. Based on the portfolio analysis, there is a great need for additional studies on risk factors and environmental triggers, disease markers and diagnosis, immunological factors, disease pathogenesis and improved animal models.
Recommendations from Workshops: The current initiative is in part based on recommendations made at the NIDCR workshop title "Enhancing Clinical Research in Sjögren's Syndrome: Critical Issues," which was held on September 25-26, 2000. The participants of the workshop identified several research areas: i) increase infrastructure by supporting an international Sjögren’s syndrome research registry and repository; ii) expand studies on the genetics of Sjögren’s syndrome and iii) encourage studies of the mechanisms leading to the disease. These recommendations have been incorporated into this initiative.