Live Long and Prosper
With her colleagues in OMRF’s Arthritis and Immunology Research Program, James focuses her work on disorders known as autoimmune diseases, conditions in which the body confuses its own tissue with outside invaders like viruses and bacteria. As a result, the immune system mistakenly unleashes its weapons against itself. These “friendly fire” attacks are at the heart of more than 40 disorders, which range from relatively common conditions like rheumatoid arthritis, multiple sclerosis, lupus and type I diabetes to rare and little-known disorders such as Wegener’s granulomatosis and scleroderma. All told, these diseases affect between 5 and 8 percent of the U.S. population—up to 23.5 million Americans—and together constitute the third leading cause of illness in this country, ranking behind only heart disease and cancer.
Normally, the immune system relies on Y-shaped proteins known as antibodies to identify and neutralize foreign pathogens that may be a threat to the body. But in autoimmune diseases, certain rogue antibodies (known as “auto”-antibodies) attack the body’s own cells.
Researchers have long known that these autoantibodies could be found in people suffering from lupus and other autoimmune disorders. Indeed, Dr. Morris Reichlin, her colleague at OMRF, had done pioneering work in understanding how and why certain people’s bodies produce autoantibodies. But, James wondered, when do autoantibodies first show up? Is it possible they actually appear in the body before the first symptoms of disease?
The idea was striking. But there was one, big hurdle: You can’t go back in time to test the blood of lupus patients before their first symptoms arose.
“If you look at the literature and all the studies being done on lupus, more than 95 percent of publications are based on data obtained after people have been diagnosed,” says James. “These early events were in many ways uncharted territory. People don’t come into the office and say, ‘I think I might get lupus in 10 years, so will you enroll me in a study and check my blood every three months until then?’”
So, reasoned James, “We needed to find a way to work backwards.”
She knew that the U.S. military collected biological samples from enlisted personnel and kept those samples, along with the individuals’ medical records, for many years. If she and her research team could comb through tens of thousands of medical records and find soldiers and sailors who eventually developed the disease, they could then request blood samples—taken prior to the onset of symptoms—and test them for autoantibodies.
It took James and the OMRF team nearly 20 years to gain access to the U.S. Department of Defense serum repository and conduct their own testing. But when they did, the results spoke for themselves: Of 130 servicemen and women who ultimately developed lupus, 88 percent of those patients had telltale autoantibodies before they showed clinical symptoms. For many of these patients, the autoantibodies appeared in the blood years before disease onset.
The work holds exciting clinical potential: Tests to detect these molecules could become a standard part of routine checkups for high-risk individuals, and a positive test could signal the need to take preventive action. Yet, cautions James, “We’re not at the point now where we have all the answers in that magic ball. There are a lot of normal, healthy individuals who will never be sick a day in their lives who still have some of these autoantibodies in their blood.” And because the causes of lupus are not yet known, preventive measures are far from guaranteed to be effective. “Fortunately, with lupus, we do have some evolving literature that shows if we could change some markers, we could change the course of the disease.”