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Genetic "Signature" Linked to Severe Lupus Symptoms

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www.ProHealth.com • February 12, 2003


A team of scientists supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and other parts of the National Institutes of Health (NIH) and the private sector, have discovered a genetic "signature" present in some patients with systemic lupus erythematosus (SLE) who develop such life-threatening complications as blood disorders, central nervous system damage and kidney failure.

Using DNA microarrays — small silicon chips that contain tiny amounts of thousands of known genes — to carry out a technique called gene expression profiling, Timothy W. Behrens, M.D., of the University of Minnesota, and his colleagues from North Shore Long Island Jewish Research Institute, analyzed thousands of genes in the peripheral blood cells of 48 lupus patients and 42 healthy controls. Surprisingly, 14 of the thousands of genes studied were linked to a subset of SLE patients with severe disease. In addition, 161 of the genes studied showed different expression patterns in SLE patients compared with healthy controls.

The 14 genes, referred to collectively as the IFN (interferon) expression signature, are turned on by the activity of interferon, a complex family of proteins involved in the regulation of immune responses. "Patients with severe SLE consistently showed higher expression levels of this IFN signature," says Dr. Behrens. The data, he says, provide strong support for developing new therapies to block IFN pathways in patients with severe lupus, and the pattern of gene expression in blood cells may be useful in identifying patients most likely to benefit from these new therapies. Gene expression profiling in blood cells may also be useful in identifying disease pathways in other autoimmune and inflammatory disorders.

"Identifying lupus patients at particular risk for severe disease before these complications arise has enormous implications for the early diagnosis and treatment of this potentially devastating disease," says NIAMS Director Stephen I. Katz, M.D., Ph.D.

Systemic lupus erythematosus (SLE), or lupus, is a chronic, inflammatory, autoimmune disease. Its symptoms range from unexplained fever, swollen joints, and skin rashes to severe organ damage of the kidneys, lungs, or central nervous system. Lupus is difficult to diagnose because it is different for every person who has it, and it affects women nine times more often than men.

Supporters of this research include: The NIH's National Center on Minority Health and Health Disparities, National Institute of Allergy and Infectious Diseases, and Office of Research on Women's Health; the Minnesota Lupus Foundation; and the Alliance for Lupus Research.

To contact Dr. Behrens, call Brenda Hudson, Media Relations Associate at the University of Minnesota, at (612) 624-5680. To contact researchers at North Shore Long Island Jewish Research Institute, call Marlena Kern, Project Coordinator, at (516) 562-1542.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and clinical scientists to carry out this research, and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS Web site at http://www.niams.nih.gov.

Reference: Baechler, E, Batliwalla F, Karypis, G, Gaffney P, Ortmann W, Espe K, Shark K, Grande W, Hughes K, Kapur V, Gregersen P, Behrens T. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. The study will appear in the online edition of the journal Proceedings of the National Academy of Sciences (PNAS) the week of February 10th.



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