University of Minnesota
Lupus research at the University of Minnesota may lead to a test that can predict damaging flares of the disease, which often leaves patients with a characteristic butterfly-shaped rash.
Toward a test for lupus
A new test may predict when lupus symptoms will worse
By Deane Morrison
A young woman looks fine to her friends, even though she's in great pain. Naturally, the friends find it hard to believe she has a life-threatening disease.
Her situation typifies systemic lupus erythematosus, an autoimmune disease caused by the body's immune system attacking its own tissues. It strikes mostly African American women of childbearing age and can cause damage—sometimes invisibly—to joints, heart, liver, kidneys, and other organs.
But capriciousness is perhaps the disease's most maddening feature.
People with lupus may go for months or years without a "flare," then wake up one day with symptoms like headache, lethargy, or lupus's hallmark butterfly-shaped rash on the face. By then it may be too late to prevent damage to organs, because often it's the damage that produces the symptoms.
The four chemokines in the U of M test are produced in response to another chemical released by an active immune system: type I interferon, which gets its name from its ability to interfere with viruses trying to replicate in the body. Its blood levels are hard to measure, however, hence the search for warning signs that yielded the four chemokines used in the test. Currently, Emily Gillespie says, at least two anti-interferon drugs for lupus are in clinical trials.
But that scenario may change, thanks to University of Minnesota researcher Emily Gillespie and her colleagues. They have found what may be chemical warning signs in the blood of patients in whom a flare is getting ready to erupt and have developed a test to detect them.
"We'd like to develop a clinical test that will help doctors know when a patient is about to go into a clinical flare," says Gillespie, an assistant professor of medicine in the University's Center for Immunology. "A test should help physicians to more effectively manage the disease and improve patient quality of life."
Flares can be treated, usually with heavy doses of steroids, but it would be much better if patients could be spared those treatments until they are really necessary, Gillespie explains.
"We'd like doctors to be able to predict what's going to happen and give patients some peace of mind or warning," she says.
Finding the red flags
The test has its roots in work by Timothy Behrens, a former U of M professor now at Genentech, who led the effort to collect blood samples and clinical data on some of the 1,000 lupus patients under the care of rheumatologist Michelle Petri of Johns Hopkins University.
Using methods Behrens developed to study gene activity in the patients' white blood cells, Gillespie and her colleagues discovered a link between severe forms of lupus and the production of chemokines—small proteins secreted when the immune system is activated. By screening 160 proteins in patients' blood, they found four chemokines whose levels were elevated in patients with active lupus.
Yet "some patients with not-so-active disease also had high levels," says Gillespie. "So we thought, could this be trouble brewing?"
Patient with a butterfly rash from lupus. Photo: Hardin MD, University of Iowa, at http://hardinmd.lib.uiowa.edu/ui/kingsbury/135.html.
To find out, they initially studied 300 patients. Among the 222 patients who felt well at the beginning of the study, blood levels of the four chemokines were low in some, but in others they were significantly elevated to varying degrees (three-fold elevations were common).
Following the patients for one year, the researchers found that those with elevated chemokines were significantly more likely to have a flare in the next year.
"The difference in symptoms between the two groups started to appear three months after the test showed elevated chemokines," Gillespie says. "Therefore, elevations may be predictive three months in advance." Repeating the experiment with 375 new patients yielded similar results.
Gillespie and her colleagues now have a simple blood test to measure levels of all four chemokines at once. The University has applied for a patent on the process and licensed the technology to a major clinical diagnostic company.
The next step is to test for evidence that treatment can avert flares in patients with elevated chemokines. If all goes well, a clinical test for the chemokines could be ready for market in a few years, Gillespie says.
The work was funded in part by the Lupus Research Institute, the Lupus Foundation of Minnesota, and the National Institutes of Health.