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LUPUS ERYTHROMATOSUS A TO Z
SOURCE: National Institutes of Health, U.S.Department of Health and Human Services: Link to NIH
Investigators have found evidence to
support several likely possibilities in the
etiology of SLE.
includes examples of research conducted in animal models that illustrate how these factors might influence the development of SLE in humans.
Immune System Dysfunction
Lupus is an autoimmune disease, so called because a person's immune system attacks her or his own tissues.
In lupus, the signs and symptoms of the disease can be attributed to damage caused directly by antibodies, the deposition of immune complexes (the combination of antigen and antibody), or cell-mediated immune mechanisms. A number of steps are involved in these mechanisms, and scientists hope to reveal the cause of lupus by examining each step.
In the process of doing so, they also may find new ways to treat lupus.
One of the hallmarks of lupus is the formation of autoantibodies, which are antibodies that react with a person's own tissue.
Autoantibodies occasionally can be present in healthy people, but they are typically found in low concentrations. Essentially all patients with lupus have autoantibodies, generally in high concentrations.
The autoantibodies found in lupus patients are often called antinuclear antibodies because they generally target the nucleic acids, proteins, and ribonucleoprotein complexes inside a cell's nucleus. Other autoantibodies in lupus patients also can bind to cell surface membranes and destroy cells directly.
Research studies have shown an association between the presence of certain autoantibodies and particular manifestations of lupus, such as kidney or skin disease.
Scientists are now trying to establish whether these autoantibodies actually cause signs or symptoms of lupus.
However, most people with lupus test positive for many different autoantibodies, so it is often very difficult to identify which autoantibodies are responsible for a specific type of tissue damage in human subjects. In lupus, the immune system produces too many autoantibodies and forms too many immune complexes.
Normally, antigen-antibody immune complexes are joined by complement, a substance in the blood that aids in the breakup and removal of immune complexes from the body.
Scientists have found that SLE patients have both inherited and acquired abnormalities in complement and complement receptors.
These deficiencies in complement may decrease the body's ability to get rid of immune complexes. Immune complexes not broken up may be deposited in various body tissues, leading to the inflammation that results in tissue damage.
Scientists continue to study
There is considerable evidence showing that genes playa role in the etiology of lupus. The extremely high occurrence of lupus in identical twins and the increased prevalence of lupus among first- and second-degree relatives of lupus patients suggests a genetic component.
In addition, when researchers look at autoantibodies typically found in a lupus patient and her or his siblings and compare them with clinical manifestations of the disease in the individuals, they find that the individuals have the autoantibodies in common more often than they have the clinical manifestations in common.
This finding indicates a genetic basis for the formation of autoantibodies that playa role in lupus.
Studies to date suggest that many different genes contribute to lupus susceptibility and that no single genetic abnormality causes the disease.
It also appears that genes may be influential in determining the type or severity of lupus.
For example, among African Americans with lupus, those with lupus nephritis are more likely than those with other clinical manifestations to have the gene for a form of a receptor that has a low efficiency for capturing immune complexes.
Other genes that have been associated with lupus in humans include
When the defective fas gene is replaced with a normal gene, the mice no longer develop signs of the disease. Scientists continue to study the genetics of lupus in humans and in animals.
If the genes that create a genetic predisposition for lupus can be identified, it may be feasible to correct genetic defects through gene therapy or other treatments.
At this time, researchers are studying
Studies have shown that the occurrence of lupus is high among both members of a pair of identical twins and much lower among nonidentical twins and other full siblings.
The fact that this concordance is not 100% among identical twins, however, suggests that environmental agents probably trigger lupus in individuals with a genetic predisposition.
Environmental factors that scientists are considering include sunlight, stress, certain chemical substances, and infectious agents such as viruses.
Exposure to the UV rays of sunlight can lead to a skin rash and exacerbate systemic manifestations of lupus. Exposure to UVB light causes certain cellular proteins to accumulate in abnormally large amounts on the cell's surface.
These proteins react with autoantibodies commonly found in people with SLE, leading to a local or systemic inflammatory response.
Doctors suspect stress is a possible trigger for lupus flares. Frequently, patients ascribe their first symptoms or worsening symptoms to a stressful event, such as divorce, death of a loved one, or job loss.
Scientists do not have a clear explanation for this phenomenon, but research is being done to find out whether stress hormones such as adrenaline or cortisone may influence the development or course of the disease. Chemical Substances A number of drugs cause a lupus-like illness in susceptible individuals, including chlorpromazine, hydralazine, isoniazid, methyldopa, and procainamide. When the offending drug is stopped, the lupus symptoms resolve. When researchers determine how these drugs cause lupus, they may be able to provide further answers on the etiology of SLE.
Many researchers suspect that infectious agents, such as viruses, may trigger lupus, somehow disrupting cellular immune function in susceptible individuals.
It is possible that the virus infects B cells (cells programmed to produce antibodies in response to specific antigens) and causes them to produce autoantibodies.
Researchers are studying various mechanisms by which viruses could result in autoimmunity.
SLE is more prevalent in women during their reproductive years. In addition, disease activity sometimes flares during pregnancy or during the postpartum period.
For these reasons, researchers have long considered that hormones may influence lupus. Some research in animals also supports this supposition. Lupus-like illnesses in animals are exacerbated when they receive female hormones.
Studies are under way to find out more about how hormones may influence the course and development of lupus.
Source: National Institutes of Health, U.S.Dept of Health and Human Services