Systemic lupus erythematous (SLE), or lupus for short, is a devastating disorder in which a patient's own immune system attacks and damages the kidneys, liver, brain, heart, spleen, joints and lungs. And despite its prevalence¿some one million Americans, 90 percent of them women, are affected¿scientists know very little about the genetics behind the disease. A new paper in today's issue of the Proceedings of the National Academy of Sciences, though, describes a genetic mutation that causes SLE-like symptoms in mice, and researchers are hopeful that it may help them better understand lupus in humans.
Jamey D. Marth and colleagues at the University of California at San Diego built their experiments around the observation that autoimmune disorders are sometimes associated with changes in N-glycans, carbohydrates found on the surfaces of cells that may play a role in helping the immune system recognize nonself versus self. So they bred mice lacking the gene for an enzyme¿alpha-mannosidase II¿that participates in the pathway leading to normal glycan production. They discovered that these animals had significantly fewer N-glycans than normal, and strangely shaped ones at that. In addition, the mice had extremely elevated levels of antibodies; kidney inflammation and scarring; excess protein and blood cells in their urine; and a higher mortality rate. Other tissues, too, were damaged in ways seen in SLE.
"This is an entirely new manner by which autoimmune disease can occur, by a gene controlling carbohydrate formation," Marth says. "These findings provide new insights into understanding autoimmune disease and suggest new diagnostic tests for possible causes of human SLE."