NEWS: UT Southwestern Researchers Locate Gene Family Involved In Determining Potential For Acquiring Lupus

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Source: University Of Texas Southwestern Medical Center At Dallas

Date: 2005-01-03

UT Southwestern Researchers Locate Gene Family Involved In Determining

Potential For Acquiring Lupus

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. 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 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;

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.

Pertsemlidis, assistant professor in the Eugene McDermott Center for Growth

and Development at UT Southwestern and Dr. ce 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.