Lupus

Disease Background

Lupus is a chronic autoimmune disease in which a person's immune system attacks the body, resulting in inflammation of various organs or tissues. The components of the immune system responsible for this effect are cells and antibodies. Antibodies, which are proteins produced by white blood cells, typically are made in response to infection caused by pathogens like bacteria and viruses. In autoimmune diseases like lupus, normal molecules of the body are mistakenly recognized by immune-system cells and antibodies and are targeted for destruction.

Depending on its form, lupus can range from a disease that primarily affects the skin to a more serious illness causing damage to multiple parts of the body. Because lupus symptoms range from skin rash and mild fatigue to organ failure, diagnosis can be difficult.

One form of lupus, Systemic lupus erythematosus (SLE) can cause inflammation of connective tissue in many parts of the body, from the joints to the kidneys. Patients with SLE can experience periods of few or no symptoms (remission) alternating with acute phases known as flares. Drug-induced lupus can develop after taking certain medications; symptoms usually go away after drug treatment is stopped.

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According to the Lupus Foundation of America, Inc., more than 16,000 Americans develop lupus each year. It is estimated that 500,000 to 1.5 million Americans have been diagnosed with the disease. Like many other autoimmune diseases, lupus occurs much more frequently in women than men. Adult women are more than 10 times more likely to suffer from lupus than adult men.

Although the causes of lupus are unknown, scientists have determined that both heredity and environmental exposures play a role. About 10 percent of those with lupus have a close relative who also suffers from the disease. Recently, scientists have identified variants of specific genes that may increase the likelihood of developing lupus. It is likely that many other yet undiscovered genes contribute to disease onset.

As is the case with other autoimmune diseases, scientists suspect that lupus onset may follow a viral or bacterial infection that somehow triggers an inappropriate immune reaction in a genetically predisposed person.

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Our Research

Overview of Hutchinson Center Research

Hutchinson Center Research includes the development of new lupus treatments and diagnostic tests as well as basic research to understand how individuals develop autoimmune diseases. Projects include:

• Center researchers are leading clinical trials that use stem-cell transplantation for treating severe forms of systemic lupus. Prior to the procedure, a patient's stem cells are collected, and cells that react against the patient's own tissue are removed. Next, patients are treated with high-dose chemotherapy and drugs to suppress their immune system. Patients then receive an infusion of the stem cells that were collected before treatment. These cells will rebuild a new, healthier immune system free of the self-reactive cells responsible for the autoimmune disease. Preliminary results from such studies have been promising.
• Hutchinson Center researchers have developed a test that may prove to be helpful in diagnosis of lupus. The test, which recently was approved by the Food and Drug Administration, is expected to help evaluate systemic lupus erythematosus (SLE) cases that were not detected by other laboratory tests. The new test detects the presence of antibodies produced by the patient to a group of molecules called SR proteins, cellular components that function in the process of gene expression.
• Hutchinson Center scientists are exploring whether small numbers of cells transferred from a fetus to mother or from mother to fetus during pregnancy are associated with autoimmune disease. Research suggests that in some cases such cells, which can persist for decades, may increase the likelihood of developing certain autoimmune diseases later in life.

Uncovering the genetic secrets of autoimmune disease

The causes of autoimmune diseases, in which the immune system begins attacking the body's own tissues, are unknown. What triggers these diseases? How do they progress? Why do they strike women much more often than men? These form the core research questions of scientists in Dr. J. Lee Nelson's laboratory. Answering them requires a variety of approaches involving collaborations with laboratory, population and clinical scientists. Her team's work is focused on systemic scleroderma, lupus and rheumatoid arthritis.

Nelson's laboratory studies focus on understanding the genetics that underlies the complex system by which the immune system distinguishes between the body's own cells and foreign invaders.

Dr. Anne Stevens, a Pediatric Rheumatologist working with Nelson, recently studied an uncommon condition of neonates called neonatal lupus syndrome. The most serious complication of neonatal lupus is permanent heart damage. Stevens found that the hearts of newborns who died consisted partly of cells that had transferred from the mother during pregnancy.

The scientists do not yet know whether the maternal cells trigger a destructive immune response by the unborn fetus, leading to heart inflammation or whether the maternal cells migrate to the heart in an attempt to repair existing damage. Either way the findings suggest the possibility of new forms of intervention for this disease.

Innovative new treatments for autoimmune diseases

A Hutchinson Center team led by Dr. Richard Nash is examining the feasibility of using stem-cell transplantation as a treatment for autoimmune diseases. These diseases are a group of about 50 ailments whose symptoms range from mild rashes to life-threatening conditions that attack major organ systems. Though each disease is different, all begin with an immune-system malfunction: destruction of the body's own normal tissue by cells that typically fight infections caused by bacteria, viruses and other micro-organisms.

The rationale for the approach is that the high-dose radiation and chemotherapy used to wipe out cancers of blood and bone marrow may be used to suppress the immune system. This high-dose therapy eliminates not only the immune system's ability to fight infection, but also its ability to attack the patient's tissues. The new immune system that regrows from selected stem cells taken from the patient's own blood will be composed of immature cells that will not include the reactive cells that trigger the immune system to attack the body. Because many autoimmune diseases begin during middle age, it is thought this stem-cell transplantation will "turn back the clock" on immune system development in these patients.

The early phase studies showed that transplantation provides promising improvement in patients' conditions, and that larger randomized comparison studies are needed to determine the long-term benefit to patients.

Nash's team is leading a multicenter trial using autologous stem-cell transplantation for scleroderma, lupus, multiple sclerosis and juvenile rheumatoid arthritis.

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New screening test for Lupus

The U.S. Food and Drug Administration has cleared for market a new screening test for lupus developed by a researcher at the Hutchinson Center. The test is considered the first significant diagnostic breakthrough for systemic lupus erythematosus, or SLE, in more than four decades. The test is expected to pick up the 20 percent of SLE cases that previously fell through the cracks because they could not be detected by the most widely used, standard screening test.

Lupus is a chronic disorder in which a person's immune system attacks the body. SLE is the most severe and potentially fatal form of the disease, which causes inflammation of connective tissue throughout the body, from the joints to the kidneys. Because symptoms range from skin rash and mild fatigue to organ failure, diagnosis can be difficult. While the majority of lupus patients produce antibodies to their own tissue that can be detected with a blood test that's been available since the early 1960s, about one-fifth of patients - those who do not make such antibodies - often go undiagnosed. The new test, developed by Dr. Mark Roth, promises to bridge that diagnostic gap.

Relevant Articles

• A precarious bond before birth — Clinical Research Division study reveals that cells transferred from mother to fetus may be linked to a rare autoimmune disorder in newborns
  
  
• Bridging the diagnostic gap for deadly form of lupus — Improved screening test developed in Roth lab receives market clearance from FDA
  
  

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