New NIAMS-Funded "SCORs" Focus on Lupus

National Institute of Arthritis and, Musculoskeletal and Skin Diseases FOR RELEASE, Wednesday, August 12, 1998, Ray Fleming, Office of Scientific and, Health Communications

Two new specialized centers of research (SCORs) have just been funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) as part of the federal medical research effort against lupus, a serious autoimmune disorder that can affect major organs and systems, frequently in young women. One of the new centers, a unique consortium of research organizations, will study the disease's genetic aspects; the other will also address genetics and immune mechanisms underlying disease flare-ups and organ damage. The two new centers are located at the University of Alabama, Birmingham, and the University of Virginia, Charlottesville.

"We are very excited about these promising new SCORs," said NIAMS Director Stephen I. Katz, M.D., Ph.D. "Our ultimate goal is to gain new knowledge about lupus in order to develop better treatments, improve quality of life, and prevent long-term illness and disability for patients with the disease." A SCOR, he added, can facilitate concentrated, coordinated basic and clinical research and can quickly translate basic advances into clinical successes and improved health care.

Lupus, or systemic lupus erythematosus (SLE), is believed to result from an interplay of genetic, environmental and hormonal factors. In lupus, the immune system is thrown out of balance and produces autoantibodies (antibodies that attack the patient's own tissues). The disease can affect many parts of the body, including the joints, skin, kidneys, lungs, heart, nervous system and blood vessels. It is characterized by periods of flare-ups and remissions. Ninety percent of lupus victims are women, most often in their childbearing years. The disease is also approximately three times more common in black women than in Caucasian women.

Robert P. Kimberly, M.D., professor of medicine and director of clinical immunology and rheumatology at the University of Alabama, Birmingham, and leader of the SCOR consortium, said that the inherited component of lupus is complex and involves subtle differences in many genes. "The challenge is to discover currently unrecognized genes that play an important role in lupus. Different combinations of genes may lead to different manifestations of the disease," he said.

The consortium's genetics research will focus on:

families with affected members regions of chromosomes associated with lupus specific genes located on chromosome 1q that may be associated with specific complications of lupus, especially renal disease determining whether specific complications of lupus are associated with certain genes. Researchers will characterize the various clinical manifestations of lupus--in the renal, cardiovascular, pulmonary, and central nervous systems--for their associations with specific lupus genes."

The approach to the genetics of lupus requires a multidisciplinary, team effort," said Dr. Kimberly. "The SCOR brings together four projects, each chosen to leverage expertise and existing resources, to accelerate the pace of discovery, and to translate fundamental discovery to the bedside." Consortium members include John B. Harley, M.D., Ph.D., Oklahoma Medical Research Foundation, Oklahoma City; Timothy W. Behrens, M.D., University of Minnesota, Minneapolis; Michelle A. Petri, M.D., The Johns Hopkins University, Baltimore, Md.; Rosalind Ramsey-Goldman, M.D., Northwestern University, Chicago, Ill.; John D. Reveille, M.D., University of Texas, Houston; and Graciela Alarcn, M.D., University of Alabama, Birmingham.

The second new SCOR is led by Shu Man Fu, M.D., Ph.D., professor of internal medicine and chief of the division of rheumatology and immunology at the University of Virginia, Charlottesville. His research team includes Kenneth S.K. Tung, M.D., Marcia McDuffie, M.D., and Felicia Gaskin, Ph.D., University of Virginia, Charlottesville; Michelle Petrie, M.D., The Johns Hopkins University, Baltimore, Md.; and Chella David, Ph.D., Mayo Clinic, Rochester, Minn.; who will study:

the genetic basis of autoimmune antibody production in transgenic mouse models early immune response in lupus in a mouse model genetic control of autoimmunity in a lupus mouse model how disease flare-ups in lupus patients correlate with new autoantibody production.

"By studying both patients and mouse models, we can translate basic observations from the mouse into patient care, and use the mouse models to test hypotheses generated from clinical observations," said Dr. Fu. "Our interactive, multidisciplinary approach will provide new insights into the pathogenesis of lupus and a rational basis for new therapy."

The National Institute of Arthritis and Musculoskeletal and Skin Diseases, a component of the National Institutes of Health, leads and coordinates the federal medical research effort in all forms of arthritis, including lupus, by conducting and supporting research projects, research training, clinical trials, and epidemiological studies, and by disseminating health and research information.