Wednesday, January 26, 2005

Genes In The Interferon System Important In Systemic Lupus Erythematosus

Two genes with very strong associations with the disease systemic lupus erythematosus (SLE) have been identified by a team of scientists headed by researchers at the Department of Medical Sciences at Uppsala University. The findings are being published today on the Web page of the highly prestigious American Journal of Human Genetics.

"These findings are probably the first genetic pieces of a huge 'interferon puzzle,' with whose help it will be possible to discover the mechanisms behind the disease SLE, and maybe other autoimmune diseases at the molecular level," says Professor Lars Rönnblom.

"It is remarkable that by studying only eleven of the some 200 genes that are seen as belonging to the interferon system, we were able to identify two genes with such clear connection to SLE," says Professor Ann-Christine Syvänen.

A few years ago Lars Rönnblom and Professor Gunnar Alm at the Swedish University of Agricultural Sciences were virtually the only researchers who claimed that the interferon system, which is involved in the body's defense against viruses, etc., was also behind the autoimmune disease SLE. Since then they have shown the importance of the interferon system in a number of works. This has led to the recognition of their hypothesis in the last year, and today it represents a white-hot field of research that has attracted a great deal of interest in the pharmaceutical industry. This picture has now been further reinforced by new findings­ - the result of multidisciplinary and international collaboration involving world experts on the interferon system, immunology, and the disease SLE, combined with world leaders in the technology for large-scale genetic analyses and statistics. The genetic and statistical analyses were performed by the doctoral student Snaevar Sigurdsson and Professor Ann-Christine Syvänen at the Center for Clinical Medical Research at Uppsala University.

The study, comprising nearly 2,000 individuals, shows that two genes in the interferon system are very strongly associated with the disease SLE. One of the genes codes for a so-called thyrosinkinase enzyme, whose function is to convey signals from interferon outside the cells to the cell nucleus.

"We found that genetic variants of thyrosinkase protect against SLE. It probably has an inhibited function that blocks the interferon effect. It is therefore possible to imagine the development of methods of treatment for SLE based on blocking the function of the thyrosinkinase enzyme," explains Lars Rönnblom.

The other gene codes for a transcription factor, which also plays an important role in regulating the interferon effect. Further functional analyses will be necessary to map the molecular mechanisms in detail.

Besides the Rheumatology Clinic at Uppsala Akademiska Hospital, hospitals in Umeå and Lund, in Sweden, and several hospitals in Finland as well as one hospital in Reykjavik provided the project with DNA samples and diagnostic information from SLE patients.

Source : Science Daily

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