The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute of Allergy and Infectious Diseases (NIAID) and the Arthritis Foundation are joining forces to support a national consortium of 12 research centers in the search for genes that determine susceptibility to rheumatoid arthritis. Genetic factors are known to play a role in predisposing people to the disease, in part because rheumatoid arthritis tends to run in families. But scientists do not yet know much about the specific genes that are involved.
In what is the largest such effort in the world, researchers participating in the North American Rheumatoid Arthritis Consortium (NARAC) hope to learn more about genes that play a role in the disease. They plan to collect medical information and genetic material (DNA) from 1,000 families nationwide in which two or more siblings have rheumatoid arthritis that began when they were between 18 and 60 years old. The project will be headed by Peter K. Gregersen, M.D., of North Shore University Hospital in Manhasset, NY. North Shore will serve as a central registry of information on sibling pairs with rheumatoid arthritis (including clinical, x-ray and laboratory data) and as a repository of serum, blood cells and DNA from patients.
"Findings from this project should give us a window onto the causes of rheumatoid arthritis, which opens up the possibility of developing new ways to diagnose and treat the disease," says Stephen I. Katz, M.D., Ph.D., director of the NIAMS. "We're very pleased to be participating in a partnership with the NIAID and the Arthritis Foundation to reach these common goals." Adds Anthony S. Fauci, M.D., director of the NIAID, "This collaborative effort promises to provide important new insights into a disease that exacts an enormous toll, both in terms of human suffering and economic costs. We look forward to participating in this important initiative to better understand this debilitating autoimmune disease."
Doyt L. Conn, M.D., Senior Vice President for Medical Affairs of the Arthritis Foundation, says: "The state of knowledge and technology today make this type of study possible. The Arthritis Foundation will not only provide financial support for the study, but through its chapters and publications will help in recruiting siblings with the disease." "This collaboration is a synergistic way to reach the goal of identifying these genes," says Debra Lappin, Esq., Chair of the Arthritis Foundation. "This is the first time in the history of the Foundation that we have joined in a partnership to support a collaborative research endeavor."
Rheumatoid arthritis, which affects over 2 million people in the United States, or about one percent of the adult population, is a potentially disabling inflammatory form of arthritis that causes pain, swelling, stiffness and loss of function in the joints, and may also affect other body systems. As rheumatoid arthritis progresses, the inflammation processówhose hallmarks include redness, swelling, warmth and pain--can cause erosion, or destruction, of bone and cartilage in the joints. The disease has a major impact on both the individual and society, causing significant pain, impaired function and disability, as well as costing millions of dollars in healthcare expenses and lost wages.
Rheumatoid arthritis is an autoimmune disease, so-called because a personís immune system attacks his or her own body tissues. Scientists donít know the cause, but they believe it results from a combination of genetic factors that make a person susceptible to the disease and some type of environmental trigger--possibly an infectious agent such as a virus or bacterium.
Treatment for rheumatoid arthritis includes a variety of medications as well as lifestyle strategies such as exercise and self-management programs. No treatment is ideal, however, and there is no cure. Development of new treatments and even ways to prevent the disease are active areas of research supported by both the NIH and the Arthritis Foundation.
The consortium's first goal in the next 3 to 5 years is to find and begin to study 1,000 families with two or more siblings who have rheumatoid arthritis and, if possible, at least one surviving parent. With help from the Arthritis Foundation, the researchers will be looking for pairs of siblings in which at least one sibling has relatively severe disease, as indicated by a hand X-ray that shows some erosion of bone. Studies show that if a person has rheumatoid arthritis, their siblings are somewhere between 2 to 10 times more likely to develop the disease than other people in the population.
Researchers at 10 of the centers (listed below), including the NIAMS intramural Arthritis and Rheumatism Branch, will collect medical information and blood samples from each patient. (Two additional centers are participating in the project but not recruiting patients.) Blood samples will be sent to North Shore University Hospital, where researchers will prepare DNA from white blood cells. The researchers will analyze DNA from affected siblings to look for genetic regions that they share more frequently than would be expected by chance--that is, more than 50 percent of the time. These shared regions are likely to contain genes that are involved in the disease.
The researchers expect to find a number of genes that are involved in causing rheumatoid arthritis. "I think itís unlikely that the same genes are going to be involved in every person," says Gregersen. "It will probably be fairly complicated, with different gene combinations involved in different people." Scientists hope that by identifying genes that play a role in the disease, they will gain a better understanding of the disease itself, which Gregersen notes is still poorly understood. Explaining the long-term goals of studies such as this, Gregersen says: "Specific treatments for rheumatoid arthritis are what we all hope will ultimately come out of this."
People with rheumatoid arthritis who have a brother or sister with the disease and are interested in participating in the study can call the coordinating center at North Shore University Hospital toll free at 800-382-4827 or send e-mail to firstname.lastname@example.org. The Web site for the consortium can be found at http://www.medicine.ucsf.edu/narac/narac.html
This project is funded by the NIH (NIAMS and NIAID) in partnership with the Arthritis Foundation, with additional funding from the NIH Office of Research on Womenís Health (ORWH).
NIAID, NIAMS and ORWH are components of the NIH, U.S. Department of Health and Human Services.
The principal investigators and participating centers in the consortium are:
Peter K. Gregersen, M.D.North Shore University Hospital Manhasset, N.Y. (coordinating center)
Mark H. Wener, M.D.*University of WashingtonSeattle, Wash.
David S. Pisetsky, M.D., Ph.D.Duke University Medical Center Durham, N.C.
Christopher Amos, Ph.D.* University of TexasM.D. Anderson Cancer CenterHouston, Texas
Richard M. Pope, M.D.Northwestern UniversityChicago, Ill.
Lindsey A. Criswell, M.D., MPHUniversity of California San FranciscoSan Francisco, Calif.
Salvatore Albani, M.D.University of California San Diego (UCSD)La Jolla, Calif.
Daniel O. Clegg, M.D.University of Utah Health Sciences CenterSalt Lake City, Utah
J. Lee Nelson, M.D.Fred Hutchinson Cancer Research CenterSeattle, Wash.
Harry W. Schroeder, M.D., Ph.D. The University of Alabama at BirminghamBirmingham, Ala. (co-principal investigator S. Louis Bridges, Jr., M.D., Ph.D.)
Michael F. Seldin, M.D., Ph.D. University of California DavisDavis, Calif.
Ronald Wilder, M.D., Ph.D. and Daniel Kastner, M.D., Ph.D.NIAMS, NIHBethesda, Md.
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