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Predicting the Severity of Lupus Attacks
Reading ‘danger signal’ sensors

Eric Greidinger, M.D., is studying immune response patterns that could help generate therapies to reduce the severity of lupus.

Like other researchers in his field, Eric Greidinger, M.D. wants to find a cure for lupus, a disease that afflicts more than one and a half million Americans. But while he spends hours in his lab studying novel approaches that will hopefully one day eradicate the devastating autoimmune disease, Greidinger wants to develop therapies that can be used today to improve the lives of people suffering from the most severe forms of the disease.

“You don’t necessarily have to have as your goal the complete cure of lupus,” says Greidinger, associate professor of medicine at the Miller School. “One other approach you can take in theory is to change the severity of lupus—change a patient’s disease from being the bad killer kind to being the mild kind.”

Greidinger, a former Princeton math major who entered medicine because he wanted to conduct work that would help sick people get well, has garnered recognition in the world of lupus research for his investigations at UM. To help advance his research, he received a $300,000 Novel Research grant (in 2006) from the Lupus Research Institute to support his work on predicting lupus organ damage and determining why some people get lupus in areas like their kidneys while others get milder forms of the disease. In October, Greidinger was awarded more funding, a $650,000 Veterans Affairs grant to further study the immune response patterns and the potential for generating new therapies that could convert severe lupus to mild lupus.

In his research, Greidinger developed a special model to assess the potential of immune system “danger signal” sensors to indicate which organs and tissues in lupus are under imminent attack. “We have gone on to show in fairly great detail that the elements of the adaptive immune system, B and T cells, remain essentially the same between the two conditions.”

The model can be influenced to get kidney disease or a non-kidney targeted form of lupus-like autoimmunity by changing the innate immune receptor (so-called “Toll-like receptors,” or TLRs) that gets activated. In the process, when one Toll-like receptor gets stimulated (TLR 7 stimulation) it produces lupus-like kidney disease, while stimulation of another Toll-like receptor (TLR 3) results in a milder form of lupus-like disease without kidney involvement. Current research is looking at how TLR stimulation accounts for this difference—information that may help doctors predict the organs at risk for lupus in individual patients and will hopefully lead to new medicines to treat the disease.