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.
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