This study will explore how genes may influence the severity of ankylosing spondylitis, a
form of arthritis that affects the spine. Patients have inflammation of the joints of the
spine, which may cause the bones of the spine to fuse, resulting in difficulty performing
Patients who developed ankylosing spondylitis after age 16 may be eligible for this study.
The onset of disease is dated to the first appearance of symptoms of inflammatory low back
pain or restricted spinal motion. Patients with a spondyloarthropathy other than AS may not
participate. Candidates will be screened with a medical history and physical examination,
blood test, and review of their medical records. They will also complete a questionnaire
about their disease symptoms and medical history.
Those enrolled in the study will return to the NIH Clinical Center at 6, 12, 18, 24, 30, 36,
42, 48, 54, and 60 months after screening for examination of the joints, measurement of
flexibility of the spine, and a blood test. They will also complete symptoms assessment and
coping questionnaires. At the first study visit (screening visit), x-rays will be taken of
the pelvis, lower back, and neck, if recent X-rays (within 1 year) are not available. These
x-ray studies will be repeated on all patients every two years during the study (at 24 and 48
months after screening).
The susceptibility to ankylosing spondylitis (AS) is largely genetically determined. Recent
studies suggest that the severity of AS is also influenced by genetic factors. The goal of
this study is to identify genes that influence the severity of AS. We hypothesize that
genetic markers of susceptibility, including human leukocyte antigen (HLA) polymorphisms, and
genes that regulate inflammation and bone formation, influence the severity of AS.
In this prospective longitudinal study, we will test the association of several genetic
markers with the severity of AS. Approximately 700 patients will be included. Measures of AS
severity will be patient-reported pain and stiffness, functional disability, patient and
physician global assessments, joint counts, number of tender entheses, spinal mobility, and
laboratory measures of inflammation. These measures will be assessed every 6 months for 5
years. We will also evaluate new laboratory tests as measures of the activity of AS.
Identifying genetic markers that are associated with differences in the severity of active
inflammation in AS will enhance our understanding of the pathogenesis of this disease by
suggesting mechanisms and pathways involved in the development of long-term damage.
- INCLUSION AND EXCLUSION CRITERIA:
1. have been diagnosed with AS by the modified New York criteria.
2. be able to read English or Spanish
Potential participants will be excluded if:
1. have a spondyloarthropathy other than AS.
2. are unable to provide informed consent.
3. anticipate not being available or able to comply with the schedule of study visits.
Study entry is not limited by sex or ethnic origin. Children will necessarily be excluded
because spondyloarthropathy developing before age 16 is considered a form of juvenile
idiopathic arthritis, and because different age-appropriate measures of functional
disability and pain would be needed.
Participants will be recruited by physician referral and self-referral. Information about
the study will be mailed to local rheumatologists and posted on the NIH website. Notices
will also be sent to local chapters of the Arthritis Foundation and the Spondylitis
Association of America. Former participants in our AS protocols will be notified of this
study by letter.
Study of first-degree relatives:
Participants will be:
1. Parent, sibling, or child (age 18 or older) of an enrolled subject.
2. Able to provide informed consent.
Family members may by asymptomatic or have signs or symptoms of AS or a condition in the
spondyloarthropathy family. There is no requirement for a minimum number of members per
family to be eligible for participation.
The accrual ceiling will be unlimited. Approximately 700 patients will be enrolled from all
study sites. Approximately 150 patients will be recruited at the NIH. Other sites
participating in this study are Cedars-Sinai Medical Center, Los Angeles, CA; the
University of California-San Francisco and University of Texas-Houston Health Sciences
Center. To ensure a sufficient sample of patients with active inflammation, enrollment in
the study will be monitored so that at least 80 patients will be included who have an ESR
of 40 mm/hr or higher at the screening visit or visit 1, or who have an elevated serum
C-reactive protein level at visit 1.