Novel route to lupus-like disea...( Researchers have knocked out a gene ...)

Researchers have knocked out a gene that codes for an enzyme involved in modifying sugar molecules on the surface of cells, producing a disorder in mice that resembles the human disease, systemic lupus erythematosus.

Their finding represents the first time that an autoimmune disease has been linked to defects in cell-surface carbohydrate chains called glycans. According to the researchers, their work suggests that faulty glycan construction may play a role in the onset of human autoimmune diseases such as lupus. Autoimmune disorders, which are caused when the body's immune system attacks its own tissues, affect about five percent of people worldwide.

The researchers, led by Howard Hughes Medical Institute investigator Jamey D. Marth at the University of California, San Diego, published their findings in the January 30, 2001, issue of Proceedings of the National Academy of Sciences.

"Until now, it's been known only by association that various autoimmune syndromes are shadowed by changes in glycosylation," said Marth. He cited, for example, that antibodies that recognize glycans are a central part of the immune system's ability to "see" foreign invaders. "However, it wasn't known whether changes in glycosylation cause autoimmune disorders," said Marth.

Past efforts to model systemic autoimmune diseases in animalsby genetically altering white blood cells, for examplehave not completely mirrored the human disorder. "In contrast, human autoimmune disease is often a long-term or chronic affliction and does not appear to be associated with similarly overactive lymphocytes," Marth said. "Patients may live many years with the disease and some do rather well, but the disease waxes and wanes. And in human lupus, intrinsic defects in the immune system, such as the presence of dysfunctional lymphocytes, do not appear."

To determine whether defects in glycosylat
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
29-Jan-2001