Sjögren’s Foundation

Sjögren's syndrome (SS) is a systemic autoimmune disease that frequently occurs concomitantly with other systemic connective tissue disorders, including rare and complex diseases such as systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). The presence of SS influences the clinical expression of the other autoimmune diseases, thus offering the unique opportunity to explore the similarities in genetic signatures, as well as common environmental and biologic factors modulating the expression of disease phenotypes. In this review, we will specifically discuss the possibility of defining "SS/SLE" and "SS/SSc" as distinct subsets within the context of connective tissue diseases with different clinical expression and outcomes, thus deserving an individualised assessment and personalised medical interventions.

Primary Sjögren's Syndrome (pSS) is an autoimmune disease involving salivary and other exocrine glands that leads to progressive lymphocytic infiltration into the gland, tissue damage, and secretory defects. The mechanism underlying this disease remains poorly understood. Here we report that mice with T-cell-targeted deletion of Stromal Interaction Molecule (STIM) 1 and STIM2 [double-knockout (DKO)] mice develop spontaneous and severe pSS-like autoimmune disease, displaying major hallmarks of the disease. In DKO mice, diffuse lymphocytic infiltration was seen in submandibular glands, a major target of pSS, by age 6 wk, progressing to severe inflammation by age 12 wk. Sjögren's syndrome-specific autoantibodies (SSA/Ro and SSB/La) were detected in the serum, and progressive salivary gland destruction and loss of fluid secretion were also seen. Importantly, we report that peripheral blood mononuclear cells as well as lymphocytic infiltrates in submandibular glands from patients with pSS demonstrated significant reductions in STIM1 and STIM2 proteins. Store-operated calcium entry was also reduced in peripheral blood mononuclear cells from pSS patients compared with those from healthy controls. Thus, deficiency of STIM1 and STIM2 proteins in T cells, and consequent defects in Ca(2+) signaling, are associated with salivary gland autoimmunopathy in DKO mice and pSS patients. These data reveal a previously unreported link between STIM1 and STIM2 proteins and pSS.

The Sjogren’s Syndrome Foundation (SSF) has developed and implemented programs critical to the health and well-being of Sjogren’s syndrome (SS) patients worldwide and that will have a profound impact on patients as well as on the diverse range of physicians who care for them. Some of the most recent initiatives include the development of Clinical Practice Guidelines, a Clinical Trials Consortium, and broad-reaching projects to increase professional education and awareness of SS. The development of Clinical Practice Guidelines will delineate, for the first time, guidelines which will lead to better decision-making in treating SS patients. Standardization of care across practices will decrease disease-related morbidity and improve patient quality of life. The launching of a Clinical Trials Consortium in SS will accelerate the availability and accessibility of drugs/biologics/over-the-counter products for treatment of SS. The implementation of numerous professional educational programs will enhance knowledge and awareness of SS on the part of health care providers. The SSF remains committed to expanding and solidifying its leadership role worldwide to improve the lives of SS patients and arm the clinician with the latest and best tools and resources for treating their patients.