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Researchers ID a Genetic Culprit in Lupus

But warn that many other factors may be at play

MONDAY, Oct. 28, 2002 (HealthDayNews) -- Researchers have discovered a gene mutation that's partially to blame for the genetic underpinnings of lupus, a disease in which the immune system attacks the body's own tissues.

Swedish scientists have identified a mutation of a gene, named PDCD1, that's more prevalent in people with lupus than in those without lupus. The mutated gene isn't doing its job, thus contributing to the malfunctioning immune system, the study found.

Previous research has shown that genetically engineered mice that lacked the PDCD1 developed a lupus-like disease.

"It's not going to be the sole cause of lupus, but it's certainly a strong movement in better understanding the disease," says Dr. Duane Superneau, chief of the section of medical genetics at the Ochsner Clinical Foundation in New Orleans.

The study appears in the October issue of Nature Genetics.

In lupus, the immune system attacks the body's own tissues, most often the skin, joints, blood and kidneys. This can cause painful and debilitating inflammation.

Researchers sequenced, or diagrammed, the PDCD1 gene in 1,000 people with lupus and 1,500 family members and non-family members who didn't have lupus.

They found that a variant of the PDCD1 gene was more prevalent in people with lupus than people without the disease. Based on statistical analysis, researchers estimate the gene variant could account for as much as 20 percent of the underlying cause of lupus.

What exactly does PDCD1 do?

Found on chromosome 2, the gene plays a role in helping the immune system distinguish itself from foreign invaders, says study author Marta Alarcón-Riquelme, an assistant professor of medical genetics at the University of Uppsala in Uppsala, Sweden.

The study found the mutated gene prevents a key protein from binding with it. The protein is in charge of regulating the gene's production of antibodies to fight invaders.

"One of the possibilities is that PDCD1 might work to inhibit antibody activation," Alarcón-Riquelme says. "This should happen normally. But when PDCD1 is not functioning, the cells are going crazy and activating and producing too many antibodies."

"What remains unknown is how this process starts and what makes it happen," she adds.

While the PDCD1 mutation is an important finding, there are surely other genes and environmental factors at play, Superneau says.

Firstly, the PDCD1 gene variant was not present in everyone who had lupus in the study, Superneau says.

Secondly, because lupus varies so much from person to person, doctors believe a single gene cannot be blamed for the disease in everyone, he adds.

While some people with the disease suffer only occasional flare-ups, lupus can be a constant and life-threatening affliction for others, he says. For some, only one organ is involved, for others, it's many organs throughout the body.

And while about 10 percent have a family member that has the disease, others don't have any family history of lupus, according to the Lupus Foundation of America.

"It's a very complicated disease," Superneau says. "There are many factors and/or many genes acting in concert to cause the disease."

Because it's such a complicated disease, diagnosing lupus is difficult, says Duane Peters, vice president for advocacy and communications at the Lupus Foundation of America.

There is no specific test for lupus. Doctors have identified 11 symptoms ranging from skin rashes to joint pain. A person who has four of the 11 is considered to have lupus, Peters says.

The hope is that the gene discovery would help lead to both earlier detection of the disease, or who's at risk of getting it, and treatments that would target the malfunction of the gene, Superneau says.

What To Do

For more information about lupus, visit the Lupus Foundation of America or the National Institutes of Health.

SOURCES: Duane Superneau, M.D., chief, medical genetics, Ochsner Clinical Foundation, New Orleans; Marta Alarcón-Riquelme, M.D., Ph.D., assistant professor, medical genetics, University of Uppsala, Uppsala, Sweden; Duane Peters, vice president, advocacy and communications, Lupus Foundation of America, Rockville, Md.; October 2002 Nature Genetics
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