The Pathogenesis and Natural History of Sjogren's Disease

Background Sjogren's Disease (SjD; formely Sjogren's Syndrome) is an autoimmune disease characterized by chronic inflammation involving the exocrine glands. Salivary and lacrimal glands are predominantly affected leading to dry mouth and dry eyes but other exocrine organs are also frequently involved. It is one of the most common rheumatic autoimmune diseases, which effects between 1-4 million Americans, predominantly women with a female to male ratio of 9:1. Sjogren s Disease may occur alone (primary SjD), or may coexist with other systemic connective tissue disorders (i.e., secondary SjD). In many cases systemic manifestations, such as fatigue, arthritis, vasculitis, lung disease, peripheral or central neuropathy and autonomic nervous system dysfunction accompany glandular involvement. Patients with systemic manifestations are at higher risk of lymphoma, the incidence of which is increased in SjD. The treatment of sicca symptoms is mainly symptomatic, whereas management of extraglandular manifestations is similar to other autoimmune diseases. The cause and pathogenesis of Sjogren's Disease is still largely unknown. In a genetically predisposed individual various environmental factors, such as viral infections, may lead to epithelial cell activation and a protracted inflammatory response with features of autoimmunity. Autoreactive lymphocytes and autoantibodies are considered important in this process although the pathogenic role of any particular autoantibody is still undefined. Although inflammation may contribute to the exocrinopathy of SjD, the relationship between inflammation and exocrine dysfunction is poorly understood. Moreover, the model does not explain many of the extraglandular manifestations of SjD patients, such as fatigue. Further studies are needed to better understand the pathogenesis of SjD. Objectives The primary objective of this study is to enable the collection of longitudinal clinical and laboratory data and biologic specimens to identify pathogenetic mechanisms of SjD by careful clinical phenotyping of SjD patients and Sjogren's-like conditions over time and collection of biologic samples for concurrent and future laboratory studies related to the pathogenesis of Sjogren's Disease. Another objective of the study is to identify biomarker candidates associated with the diagnosis, severity, prognosis, or organ involvement in SjD. The protocol will enable the study of the genetic basis and the mechanistic aspects of immunologic and non-immunologic abnormalities of SjD and their associations with various clinical phenotypes. Eligibility Criteria The study will enroll 300 subjects with Sjogren s Disease or Sjogren's-like conditions. Subjects aged 16-years or older fulfilling European American Consensus Criteria for Primary or Secondary Sjogren s Disease are eligible for the study. Selected subjects with incomplete Sjogren's Disease or who are excluded from the European American criteria may also be eligible. Screening will be done on the Characterization of Diseases with Salivary Gland Involvement protocol (15-D-0051) prospectively or on the previous screening protocol (84-D-0056). Description of the Study This is a longitudinal observational study. All subjects will have core evaluations (approximately biannually) during a 10-year period. Additional evaluations may be required if there is a significant change in the clinical condition of subjects likely related to SjD or sicca syndrome or to provide additional research samples or clinical data for the pathogenesis studies. Clinical data will be collected through questionnaires, personal interviews, physical examination, laboratory testing and imaging studies. The core evaluation will include a complete medical history and physical examination and a complete oral and dry eye evaluation. Blood, saliva and biopsy samples will be stored and used for laboratory research studies aimed at the pathogenesis of Sjogren s Disease. Samples labeled with a code without any personal identifiers may be shared with researchers in and outside the NIH. DNA will be collected for genetic studies related to Sjogren's' syndrome and related conditions.