Environmental Risk Factors for the Anti-Synthetase Syndrome

Location:

Rochester, Minn.

Trial status:

Open for Enrollment

Why is this study being done?

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.

Who is eligible to participate?

- INCLUSION CRITERIA: There are no gender, ethnic or age restrictions to enrollment in the study. The inclusion criteria for enrollment of myositis subjects are: 1. Diagnosis of myositis based on criteria for possible, probable or definite PM or DM, with or without other connective tissue diseases, documented within 24 months of enrollment (using the most recent diagnosis date to define the 24 month period). 2. CXR to assess possible ILD and assign the subject to the presumptive anti-synthetase positive or negative category if clinically indicated. 3. Children must be at leas t two years of age . 4. Able and willing to give informed consent, to complete the questionnaires and to donate blood samples (in case of children at least 2 years of age but < 18 years of age , parent/legal guardian must be willing and able to provide informed consent and child must provide assent). The inclusion criteria for controls are: 1. Friends or, if friends are not available, cousins of the anti-synthetase positive myositis patient, or, if friends or cousins are not available, volunteers from the general community (such as the NIH Normal volunteer program), gender- and age- (within 5 years for minors and within 10 years for adults) matched, who is living as close as possible to the geographic area of the myositis patient. 2. Controls should be without a recognized autoimmune disease or ILD. 3. Able and willing to give informed consent, to complete the questionnaires and to donate blood samples (in case of children 2 years of age but < 18 years of age, parent/legal guardian must be willing and able to provide informed consent) and child must provide assent). EXCLUSION CRITERIA: The exclusion criteria for myositis subjects are: 1. Cancer-associated myositis (cancer diagnosed within 2 years of the diagnosis of myositis). 2. Inclusion body myositis. 3. Myositis that has clearly developed as the result of a drug, toxin or other exposure and has resolved after discontinuation of the exposure to that agent. 4. Children less than 2 years of age. The exclusion criteria for all protocol subjects are: 1. Medical illness that in the judgment of the investigators does not allow safe blood draws or other clinical evaluations needed for study participation. 2. Cognitive impairment. 3. Not able or willing to give informed assent or consent. 4. Children less than 2 years of age .

Last updated:

11/11/2014

NCT ID:

NCT01276470

IRB Number:

10-007479