A team headquartered at UCLA and Cedars-Sinai Research Institute has narrowed the search for a gene causing the mysterious autoimmune disease lupus to a small region of the vast human genome.
The finding should lead to better understanding of the causes of the disorder and eventually, to new treatments. Lupus affects as many as 2 million Americans, according to the Lupus Foundation of America.
In the disease, known clinically as systemic lupus erythematosus, the body attacks itself, damaging a broad variety of internal organs.
Until the current findings, reported today in the Journal of Clinical Investigation, were made, researchers had little idea what causes lupus, although it is clearly a combination of genetic susceptibility and environmental factors.
Experts are particularly enthusiastic about the new findings because the association of the disease to one segment of Chromosome 1 was observed in whites, Asians and African Americans alike.
“The finding that this gene appears to play a role across ethnic groups is very exciting. It suggests that this is going to be an important gene for explaining what causes lupus,” said Dr. Susana Serrate-Sztein of the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
Like arthritis, multiple sclerosis and diabetes, lupus is a disease of the immune system gone awry. For reasons that are not clear, antibodies that should be defending the body against bacteria and viruses attack internal organs instead, causing them to deteriorate painfully.
Although many organs may be affected, victims usually suffer from swollen and achy joints, extreme fatigue, anemia, kidney damage and painful breathing. Many victims also get rashes, especially a wolf-like mask across the cheeks and nose that gives the disease its name (lupus is Latin for wolf). Nine out of 10 sufferers are women.
Researchers have long suspected a genetic susceptibility, according to Dr. Brian L. Kotzin of the National Jewish Medical and Research Center in Denver. In an editorial in the same journal, he noted that children with a sibling who has lupus have about 20 times the normal 1% to 2% risk of developing the disease. But, he added, scientists had no idea which genes were involved.
In the new study, rheumatologist Betty P. Tsao of UCLA and her colleagues at Cedars-Sinai and elsewhere analyzed DNA from 52 sibling pairs from 43 families of white, African American and Asian descent. Based on studies in mouse models of the disease, they concentrated on one end of Chromosome 1, one of the 23 pairs of chromosomes that make up the human genetic blueprint.
They concluded that the susceptibility gene lies in a narrow region of Chromosome 1 that contains about 500 genes--out of the estimated 100,000 total genes that make up a human. They are now working to identify the specific gene involved.
Finding the actual gene should enable researchers to develop new therapies targeting the biochemical defect that causes lupus.
“I expect that there will be a gene discovered that we did not understand had anything to do with this particular disease or the immune response in general,” said Dr. Bevra H. Hahn of UCLA. “We will have whole new ideas [about why people get the disease]. That should result in some kind of therapeutic intervention, to target the mechanisms that have gone awry.”