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IRCM scientist demonstrates basic active mechanism of immune-system cells


Major breakthrough in the treatment of autoimmune diseases

In the upcoming issue of Immunity, a highly regarded journal put out by the Cell group, Dr. André Veillette, a scientist at the Institut de recherches cliniques de Montréal (IRCM), and his team will publish the results of a study that could revolutionize the treatment of autoimmune diseases, such as juvenile diabetes, lupus, and rheumatoid arthritis. Contemporary medicine has to date achieved only mixed results in dealing with these diseases, which affect hundreds of thousands of Canadians.

Dr. Veillette’s team has discovered one of the basic mechanisms that control the production of antibodies by immune-system cells known as B lymphocytes or B cells. In subjects with autoimmune diseases, these lymphocytes, which are also normally responsible for fighting infection, are hyperactive, causing antibodies secreted by superactivated lymphocytes to turn against the body. This leads to the development of autoimmune diseases, which are characterized by debilitating inflammation and advanced tissue damage. Dr. Veillette’s breakthrough identifies a cascade of molecular reactions involved in this type of damage, providing new therapeutic targets that could be used to reduce attacks on the pancreas in juvenile diabetes, on the kidneys in lupus, and on the joints in rheumatoid arthritis.

This publication is a major milestone for Dr. Veillette, an internationally recognized expert on the identification of molecular mechanisms that control the immune response. Initial findings were published in Nature Immunology in 2001, followed by an article in Nature Cell Biology in 2003. The article slated for publication in the November 2004 issue of Immunity provides genetic evidence of the importance of the molecular mechanism discovered by Dr. Veillette’s team.

More precisely, this discovery links three elements: a receptor (or "sensor") located on the surface of the lymphocytes, known as SLAM; an adaptive protein (or "molecular relay") located in the cell, known as SAP; and FynT, an enzyme that is also located within the cell. Using mice with genetically mutated SLAM, SAP or FynT proteins, Dr. Veillette provided evidence of the importance of links among the three proteins. It should also be noted that SAP protein mutations occur in humans, causing a fatal immune dysfunction known as "X-linked lymphoproliferation" (XLP). Dr. Veillette’s discovery paves the way for the development of SLAM, SAP or FynT inhibitors, which could block excessive immune responses observed in patients with autoimmune diseases.

François Brochu | EurekAlert!
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