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Consortium to Detect Causes for Arthritis of the Spine

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By News release • • April 8, 2000

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) has awarded $4.5 million to establish the North American Spondylitis Consortium (NASC) to search for genes that determine susceptibility to ankylosing spondylitis (AS), a rare but painful inflammatory disease of the spine, primarily affecting men. The gene HLA-B27 is known to be linked to AS; however, researchers believe that there are additional genes associated with its pathogenesis (the origin and course of a disease).

The consortium, made up of researchers with a background in clinical and genetic research in AS, hopes to learn more about genes that play a role in the disease. They plan to collect medical information and genetic material (DNA) from 400 families nationwide in which two or more siblings have AS. The project will be headed by John D. Reveille, M.D., of the University of Texas-Houston Health Science Center, along with investigators at nine other research centers and staff from the Spondylitis Association of America.

“We are encouraged by the possibilities for development of new approaches for the diagnosis and treatment of ankylosing spondylitis as a result of this research project," says Stephen I. Katz, M.D., Ph.D., director of the NIAMS.

Ankylosing spondylitis, also known as arthritis of the spine, is a rheumatic disease that causes inflammation of the tendons and ligaments around the bones and joints in the spine. The result is pain and stiffness, especially in the lower back. While AS primarily affects the spine, it can also cause inflammation in the hips, shoulders and knees. AS usually begins in late adolescence or early adulthood. The disease is primarily diagnosed in men; however, recently, diagnosis of AS among women has increased.

Treatment for AS is designed to reduce inflammation in the joints and maintain flexibility. Therapy includes nonsteroidal anti-inflammatory drugs such as ibuprofen, disease-modifying drugs such as sulfasalazine and methotrexate, and to a limited degree, antibiotics. In cases of spinal fusion, surgery is used to straighten the back and allow a person to stand upright; however, restoring original flexibility and function is not possible. There is no cure.

"Recent familial studies show genes other than HLA-B27 have possible implications for AS, " said Dr. Reveille, head of the coordinating center leading the study. "Mapping these genes may shed fundamental light on AS and other autoimmune diseases," he added. HLA-B27 is a part of a family of genes known to play a role in the function of that part of the immune system known as the major histocompatibility complex (MHC).
The consortium's goals begin with the recruitment of families in which two siblings have been diagnosed with AS. The Spondylitis Association of America will have a major role in recruitment of patients and also will maintain a central registry of information on families and sibling pairs with AS (including clinical, x-ray and laboratory data). At the University of Texas-Houston Health Science Center, researchers will establish a bank of sera (or blood), genomic DNA and frozen lymphocytes (or white blood cells) from the affected and unaffected sibling pairs, and–when available–both their parents.

Through genetic typing methods, researchers will search for additional alleles (or alternative forms of a gene) within the MHC that may contribute to predisposition of AS. In addition, they will conduct a genome-wide search for sibling pairs affected and unaffected by AS and map genes linked to AS that exist outside of the MHC. Finally, the research team hopes to identify, from newly mapped candidate genes, mutations and their effect on disease severity.
"We are pleased to be a part of this active ongoing partnership between an outstanding research team and the Spondylitis Association of America. This partnership is key to ensuring the success of this important project," said Dr. Katz.

Source: The National Institute of Arthritis and Musculoskeletal and Skin Diseases

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