Systemic Lupus Erythematosus

U.S Department of Health and Human Services
National Institutes of Health

National Institute of Arthritis and Musculoskeletal and Skin Diseases

Current Research

Lupus is the focus of intense research as scientists try to determine what causes the disease and how it can best be treated. Some of the questions they are working to answer include: Why are women more likely than men to have the disease? Why are there more cases of lupus in some racial and ethnic groups? What goes wrong in the immune system, and why? How can we correct the way the immune system functions once something goes wrong? What treatment approaches will work best to lessen lupus symptoms? How do we cure lupus?

To help answer these questions, scientists are developing new and better ways to study the disease. They are doing laboratory studies that compare various aspects of the immune systems of people with lupus with those of other people both with and without lupus. They also use mice with disorders resembling lupus to better understand the abnormalities of the immune system that occur in lupus and to identify possible new therapies.

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a component of the Department of Health and Human Services' National Institutes of Health (NIH), has a major focus on lupus research in its on campus program in Bethesda, Maryland. By evaluating patients with lupus and their relatives, researchers oncampus are learning more about how lupus develops and changes over time. The NIAMS also funds many lupus researchers across the United States. Some of these researchers are studying the genetic factors that increase a person's risk for developing lupus. To help scientists gain new knowledge, the NIAMS also has established Specialized Centers of Research devoted specifically to lupus research. In addition, the NIAMS is funding lupus registries that gather medical information as well as blood and tissue samples from patients and their relatives. This gives researchers across the country access to information and materials they can use to help identify genes that determine susceptibility to the disease.

Identifying genes that play a role in the development of lupus is an active area of research. For example, researchers suspect that a genetic defect in a cellular process called apoptosis, or "programmed cell death," exists in people with lupus. Apoptosis is similar to the process that causes leaves to turn color in autumn and fall from trees; it allows the body to eliminate cells that have fulfilled their function and typically need to be replaced. If there is a problem in the apoptosis process, harmful cells may stay around and do damage to the body's own tissues. For example, in a mutant mouse strain that develops a lupus-like illness, one of the genes that controls apoptosis is defective. When it is replaced by a normal gene, the mice no longer develop signs of the disease. Scientists are studying what role genes involved in apoptosis may play in human disease development.

Studying genes for complement, a series of proteins in the blood that play an important part in the immune system, is another active area of lupus research. Complement acts as a backup for antibodies, helping them destroy foreign substances that invade the body. If there is a decrease in complement, the body is less able to fight or destroy foreign substances. If these substances are not removed from the body, the immune system may become overactive and begin to make autoantibodies.

Recent large studies of families with lupus have identified a number of genetic regions that appear to be associated with risk of SLE. Although the specific genes and their function remain unknown, intensive work in mapping the entire human genome offers promise that these genes will be identified in the near future. This should provide knowledge of the complex factors that contribute to lupus susceptibility.

NIAMS-funded researchers are uncovering the impact of genetic, socioeconomic, and cultural factors on the course and outcome of lupus in Hispanics, African Americans, and Caucasians. Preliminary data show that African American and Hispanic lupus patients typically have more kidney damage compared with Caucasians. In addition, NIAMS-funded researchers found that African American lupus patients have more skin damage compared with Hispanics and Caucasians, and that the death rate from lupus is higher in African Americans and Hispanics compared with Caucasians.

It is thought that autoimmune diseases, such as lupus, occur when a genetically susceptible individual encounters an unknown environmental agent or trigger. In this circumstance, an abnormal immune response can be initiated that leads to the signs and symptoms of lupus. Research has focused on both the genetic susceptibility and the environmental trigger. Although the environmental trigger remains unknown, microbial agents such as Epstein-Barr virus and others have been considered. Researchers also are studying other factors that may affect a person's susceptibility to lupus. For example, because lupus is more common in women than in men, some researchers are investigating the role of hormones and other male-female differences in the development and course of the disease. A current study funded by the NIH is focusing on the safety and effectiveness of oral contraceptives (birth-control pills) and hormone replacement therapy in women with lupus. Doctors have worried about the wisdom of prescribing oral contraceptives or estrogen replacement therapy for women with lupus because of a widely held view that estrogens can make the disease worse. Oral contraceptives and estrogen replacement therapy do not, as once feared, appear to intensify lupus symptoms. Scientists do not know the effects of oral contraceptives on women with antiphospholipid antibody syndrome.

Patients with lupus are at risk of developing atherosclerotic vascular disease (hardening of the blood vessels that can cause heart attack, angina, or stroke). The increased risk is due partly to having lupus and partly to steroid therapy. Preventing atherosclerotic vascular disease in lupus patients is a new area of study. NIAMS-funded researchers are studying the most effective ways to manage cardiovascular risk factors and prevent cardiovascular disease in adult lupus patients.

In childhood lupus, researchers are evaluating the safety and effectiveness of drugs called statins that lower LDL (or bad) cholesterol levels as a method of preventing fat buildup in the blood vessels.

One out of five lupus patients experiences symptoms such as headaches, dizziness, memory disturbances, stroke, or changes in behavior that result from changes in the brain or other parts of the central nervous system. Such lupus patients have what is called "neuropsychiatric" lupus. NIAMS-funded scientists are applying new tools such as brain imaging techniques to discover cellular activity and specific genes that may cause neuropsychiatric lupus. By uncovering the mechanisms responsible for central nervous system damage in lupus patients, researchers hope to move closer to improved diagnosis and treatment for patients with neuropsychiatric lupus.

Researchers are focusing on finding better treatments for lupus. A primary goal of this research is to develop treatments that can effectively minimize the use of corticosteroids. Scientists are trying to identify combination therapies that may be more effective than single treatment approaches. Another goal is to improve the treatment and management of lupus in the kidneys and central nervous system. For example, a 20- year study supported by the NIAMS and the NIH found that combining cyclophosphamide with prednisone helped delay or prevent kidney failure, a serious complication of lupus.

On the basis of new information about the disease process, scientists are using novel "biologic agents" to selectively block parts of the immune system. Development and testing of these new drugs, which are based on compounds that occur naturally in the body, comprise an exciting and promising new area of lupus research. The hope is that these treatments not only will be effective, but also will have fewer side effects. Preliminary research suggests that white blood cells known as B cells may play a key role in the development of lupus. Biologics that interfere with B cell function or block the interactions of immune cells are active areas of research. These targeted treatments hold promise because they have the advantage of reduced side effects and adverse reactions compared with conventional therapies. Clinical trials are testing the safety and effectiveness of rituximab (also called anti-CD20) in treating people with lupus. Rituximab is a genetically engineered antibody that blocks the production of B cells. Other treatment options currently being explored include reconstructing the immune system by bone marrow transplantation. In the future, gene therapy also may play an important role in lupus treatment.

Hope for the Future

With research advances and a better understanding of lupus, the prognosis for people with lupus today is far brighter than it was even 20 years ago. It is possible to have lupus and remain active and involved with life, family, and work. As current research efforts unfold, there is continued hope for new treatments; improvements in quality of life; and ultimately, a way to prevent or cure the disease. The research efforts of today may yield the answers of tomorrow, as scientists continue to unravel the mysteries of lupus.