Environmental Risk Factors for the Anti-synthetase Syndrome

Most autoimmune diseases are thought to develop as a result of chronic immune activation and dysregulation after selected environmental exposures in genetically susceptible individuals. Based on prior studies suggesting roles for noninfectious and infectious agents in the development of myositis, as well as the known clinical, epidemiologic and genetic differences among phenotypes, we hypothesize that different myositis phenotypes are triggered by different environmental exposures in genetically susceptible individuals. One phenotype that is particularly well-defined clinically and genetically, and for which environmental triggers are likely, is myositis associated with anti-synthetase autoantibodies (defined as the anti-synthetase syndrome). These patients have an acute myositis onset in the spring of the year and also tend to develop fevers, elevated white blood cell counts, arthritis and interstitial lung disease. Although these features are consistent with an environmental trigger for the anti-synthetase syndrome, and although case reports and animal models suggest infectious or noninfectious agents may play a role, no study has systematically assessed environmental agents in this population. In collaboration with multiple centers, we plan to test the hypothesis that certain environmental exposures are associated with the anti-synthetase syndrome and differ from those seen in matched controls and in myositis patients without the anti-synthetase syndrome. The specific aims of this study are to: 1) determine whether selected noninfectious environmental exposures are more common preceding disease onset in 150 recent-onset (defined as within 24 months of meeting criteria for possible, probable or definite myositis) myositis patients with the anti-synthetase syndrome, compared with 150 control subjects without autoimmune disease (1:1 matched with the patients), and compared with 150 recent-onset myositis patients without the anti-synthetase syndrome; and 2) determine whether selected infectious agents can be detected more frequently in blood samples of recent-onset anti-synthetase syndrome patients compared with matched controls, and in blood or biopsy samples from recent-onset anti-synthetase myositis patients compared with recent-onset myositis patients without the anti-synthetase syndrome. Medical histories, concurrent conditions and environmental questionnaire information will be collected from all participants. Subjects will undergo a clinical, laboratory and immunologic assessment to document current diagnoses, disease manifestations and severity. A chest x-ray, high resolution computed tomography (HRCT) of the chest, pulmonary function tests, bronchoalveolar lavage, and muscle and lung biopsies will be performed as clinically indicated. Blood DNA and RNA sera, biopsy and house dust repositories will be created for current and future investigations.