Research

Research

Immunological Research Spells Hope for Lupus Treatment


	Lupus can affect the joints or other parts of the body.

Until recently, the main breakthrough in the treatment of lupus came 50 years ago when corticosteroids were introduced to treat the disease. Prior to that time, patients typically died within five years of diagnosis. With steroid treatment, lives were extended, and 90 percent of patients now survive longer than five years.

According to Dr. Keith Elkon, adjunct professor of immunology and professor and head of UW Medicine's Division of Rheumatology, systemic lupus erythematosus (commonly called lupus) is the prototypic autoimmune disease. Nine out of 10 patients are young women. This chronic disease commonly affects the skin, joints and kidneys, but almost any organ can be involved, including blood vessels and the brain.

While providing useful therapy for lupus, steroids have serious side effects including joint deterioration, thinning bones, and weight gain. Steroid treatment also makes a patient more susceptible to diabetes, high blood pressure, and infections.

In the past few years, clinical and laboratory researchers have devised potential new treatments for lupus. Under Elkon's initiative, UW Medicine has opened a lupus clinic to provide care and to offer new therapies. A promising approach to treatment explores drugs that block or inhibit the B lymphocyte cells that produce abnormal antibodies. The UW lupus clinic has applied to be a site for trials of these treatments.

Elkon's team also is working with scientists at the UW Genome Center to define the molecular and genetic basis of lupus and other autoimmune diseases such as rheumatoid arthritis and scleroderma, a condition that hardens the skin and small blood vessels. Success in discovering the causes of these diseases is expected to suggest additional treatments.

Several suspected genes are being studied for their possible role in lupus. Scientists are trying to identify suspicious gene sequences within the DNA of affected patients. Researchers then will test to see if the questionable sequence differs from that in the DNA of normal cells.

Elkon's research also explores the way lupus responds to the body's own proteins. A healthy immune system normally fights invaders such as infections. In a patient with lupus, the immune system turns against the body. Elkon said the clue to fighting lupus and other autoimmune diseases would be to discover how the immune system gets misdirected and responds to molecules within the cell.

Researchers have found that a major antibody in patients with lupus is directed against DNA. This anti-DNA antibody has been associated with kidney disease. The next step is to learn how antibodies to DNA are formed.

For example, researchers are examining how dead cells in the body are processed and presented to the immune system. Through apoptosis, more than a billion cells in the body die every day. As part of the body's normal homeostatic mechanism, new cells are created to replace the ones that have died.

Elkon believes that the body's defective handling of dead cells containing DNA could be a cause of lupus. Normally, dead cells are released in a tight package. If the cell package ruptures, the contents may instigate inflammation and an abnormal immune response.

Millions of people in the United States, mostly women, suffer from lupus and similar autoimmune diseases. Roughly one in every 2,000 women in the United States has lupus, and their relatives are at increased risk of developing the disease. About 2.5 million Americans have rheumatoid arthritis, and approximately 150,000 have scleroderma.