UT Southwestern researchers locate gene family involved in determining potential for acquiring lupus

December 14, 2004

DALLAS - Dec. 15, 2004 - Researchers at UT Southwestern Medical Center at Dallas have found a gene family involved in determining the potential for acquiring lupus, a debilitating autoimmune disease that affects more than one million Americans.

"Our findings indicate genetic susceptibility to lupus results from imbalance between genes that increase and genes that suppress the immune system's responsiveness," said Dr. Ward Wakeland, director of the Center for Immunology and the Harold C. Simmons Arthritis Research Center at UT Southwestern and senior author of the study in today's issue of Immunity. "Individuals with increased risk for lupus may simply have the misfortune of expressing a 'bad' combination of versions of genes that are 'good' for resistance to infectious diseases."

Systemic lupus erythematosus (SLE) is an autoimmune disease causing the immune system to attack the body's own tissue and organs, including the joints, kidneys, heart, lungs, brain, blood and skin. The Lupus Foundation of America estimates approximately 1.5 million Americans have the disease, which affects all age groups. It is 10 to 15 times more likely in adult women than adult men.

In its study of a mouse strain that develops autoimmunity similar to human SLE, Dr. Wakeland's research team identified a cluster of genes, the SLAM/CD2 family, occurring in the same region of the human genome associated with genetic susceptibility to the disease. The genes played a crucial role in the disease's development in the mice, but only when they were expressed in specific combinations with other genes.

"The SLAM/CD2 family interacts with sets of highly variable genes, which can provide a pathway toward disease," said Dr. Wakeland.

In addition, the researchers linked this gene family to resistance to infectious diseases. The latest findings follow an earlier discovery by Dr. Wakeland and his colleagues of four genes that can halt lupus.

These "suppressor" genes - Sles1, Sles2, Sles3 and Sles4 - can block the disease even if the susceptibility gene family is active.

"For example, Sles1 specifically suppresses the autoimmune activity associated with the SLAM/CD2 gene family found in the mouse model," Dr. Wakeland said. "With the identification of SLAM/CD2, we now have half of the combination of genes that can either lead to or suppress severe disease. Once we fully characterize Sles1, we'll have the complete picture."

Researchers in the Center for Immunology are currently working with faculty in the Division of Rheumatology and the Simmons Arthritis Research Center to expand analysis of these genes and their functions into humans with SLE, as well as individuals who may be at increased risk for developing the disease so they can be identified earlier.

"The way the disease is treated now is through a broad spectrum of drug therapies that basically suppress the entire immune system," Dr. Wakeland said. "Patients with lupus under this therapy are at risk to develop infectious diseases because their immune system is completely impaired. If we can understand what the suppressor gene is doing to block SLAM/CD2, we may be able to tweak the immune system back into normal balance."

Other Center for Immunology contributors to the Immunity study were Dr. Amy Wandstrat, assistant instructor; Xiang-Hong Tian, senior research associate; Charles Nguyen, Medical Scientist Training Program student; Alice Chan, MSTP student; Nisha Limaye, student research assistant; Srividya Subramanian, student research assistant; and Dr. Young-Sun Yim, former postdoctoral researcher. Dr. Harold Garner, professor of biochemistry, and Dr. Alexander Pertsemlidis, assistant professor in the Eugene McDermott Center for Growth and Development at UT Southwestern and Dr. Laurence Morel of the University of Florida School of Medicine also contributed.
Research was supported by grants from the National Institutes of Health, the Alliance for Lupus Research, the Lupus Research Institute, the Arthritis Foundation and the National Institute of Allergy and Infectious Diseases.

This news release is available on our World Wide Web home page at http://www8.utsouthwestern.edu/utsw/cda/dept37389/files/198829.html

To automatically receive news releases from UT Southwestern via e-mail, subscribe at www.utsouthwestern.edu/receivenews

UT Southwestern Medical Center

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.