Environmental Risk Factors for the Anti-synthetase Syndrome

Conditions:Skin and Soft Tissue Infections, Infectious Disease, Orthopedic, Nephrology
Therapuetic Areas:Dermatology / Plastic Surgery, Immunology / Infectious Diseases, Nephrology / Urology, Orthopedics / Podiatry
Age Range:2 - 120
Start Date:January 12, 2011
Contact:Meghana Vijaysimha
Phone:(301) 451-6031

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Environmental Risk Factors for the Anti-Synthetase Syndrome


- Like other complex diseases, autoimmune diseases are the result of numerous causes,
including genetic and environmental factors. Some researchers believe that people who
are susceptible to autoimmune disorders develop them when the body reacts to
environmental or other factors by creating white blood cells that attack the body s own
tissues, which then progresses to autoimmune diseases. These immune-triggered disorders
can overlap with one another to some extent, but most autoimmune diseases have certain
distinct triggers.

- The autoimmune disorder myositis weakens the muscles and may cause other health
problems. Environmental exposures associated with myositis include ultraviolet
radiation, stressful life events and muscle overexertion, collagen implants, infections
such as retroviruses and streptococci bacteria, and certain drugs and chemicals. Some
individuals with myositis also produce proteins in the blood called autoantibodies that
react with certain parts of the person s own cells, called synthetases, which are
involved in making new proteins. A syndrome called the anti-synthetase syndrome, which
includes myositis and lung disease, is associated with having the anti-synthetase
autoantibodies. Researchers are interested in studying differences in environmental
exposures in individuals with myositis. This study is being conducted to determine if
persons with the anti-synthetase syndrome have had different environmental exposures
before disease onset compared with other patients with myositis who do not have this
syndrome and also compared with healthy volunteers.


- To determine whether selected infectious and noninfectious environmental exposures are more
common in individuals who have myositis with the anti-synthetase syndrome, compared with
healthy volunteers.


- Individuals who have been diagnosed with myositis (with or without anti-synthetase
autoantibodies), and healthy volunteers without autoimmune disorders.


- Participants will be screened with a full medical history and physical examination, and
will provide blood, urine and house dust samples.

- Participants will complete questionnaires about their medical history and the types of
exposures they have had at work, at home, and elsewhere. Participants who have myositis
will also be asked about certain infections, heavy exercise or physical exertion, sun
exposure, tobacco and alcohol use, and stressful events prior to being diagnosed with
the disease. Healthy volunteers will be asked about the same exposures before the date
of diagnosis of disease of the myositis subject to which they have been matched.

- Participants will receive a kit that contains instructions and a filter to be put onto
their vacuum cleaner to collect house dust in the bedroom. This dust will be kept for
possible future analyses of infectious or toxic agents based on the other results from
the study.

- Individuals with myositis will have other tests as clinically indicated, including lung
function tests and imaging studies.

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.


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).


The exclusion criteria for myositis subjects are:

1. Cancer-associated myositis (cancer diagnosed within 2 years of the diagnosis of

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 .

HIV considerations:

HIV is not an exclusion for affected participants in this study for the two following

- It has no impact on study procedures or tests.

- It may be one of the viral risk factors we are investigating.
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