Scientists have discovered the first example of a gene solely responsible for an autoimmune disease, a type of disorder in which the immune system attacks the body. The finding, announced 31 October at the annual meeting of the American Society for Human Genetics in Baltimore, Maryland, is expected to lead to a better understanding of many forms of autoimmunity, including common ones such as multiple sclerosis and rheumatoid arthritis, whose causes are largely mysterious.
The findings pinpoint the gene behind a rare disease with a jawbreaking name: autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). In the malady, a victim's immune system attacks hormone-producing organs such as the pancreas and the thyroid, parathyroid, and adrenal glands, often rendering them nonfunctional. People with APECED also often suffer from chronic fungal infections in their mouths and other mucous membranes, and hair loss. Unlike other autoimmune disorders with associated risk factors, APECED is clearly caused by a mutation in a single gene, based on analyses of affected families.
The search for the gene began in Finland, whose isolated population has often been studied for its elevated rate of rare genetic diseases. Leena Peltonen, of the National Public Health Institute in Helsinki, and her colleagues, studied 14 Finnish families with 23 members afflicted with APECED. By 1994, Peltonen's group had homed in on a region on chromosome 21 that likely contained the mutated gene. After that publication, Peltonen teamed up with Marie-Laure Yaspo and her group at the Max Planck Institute for Molecular Genetics; and a second international collaboration, led by Nabuyoshi Shimizu in Japan, Stylianos Antonarakis in Switzerland, and Kai Krohn in Finland, began hunting for the gene. The race was on, with the two teams probing for candidate genes in that region to determine which bore the APECED mutations.
Now the race has ended in a tie. Both groups announced they have found the gene and will soon publish their results. They don't know the purpose of the protein it encodes. However, in the presentations, speakers for both teams said that two stretches of the gene code for so-called zinc fingers--protein structures that insert themselves into the grooves of DNA--suggesting that the encoded protein probably turns other genes on and off. The teams disagree, however, about where the gene is expressed. Peltonen's group found that the gene is turned on in "a wide variety of tissues," while Shimizu's group found it active significantly only in the thymus, lymph nodes, and fetal kidney cells--all areas important for the development of the immune system's T cells.
The find is a welcome booster shot for autoimmune research. "We don't have very many insights into autoimmune disease," says Victor McKusick, of Johns Hopkins University, who is compiling a massive database of inherited characteristics.