In research published in the May Journal of Clinical Investigation, a team headed by Senior Staff Scientist Derry Roopenian discovered that a normally functioning protein, referred to as FcRn, plays an important role in promoting arthritis, a common form of autoimmune disease.
In total, 80 known autoimmune diseases strike 10 million Americans, and constitute one of the leading causes of disability among women. Women comprise 75 percent of patients with autoimmune disease.
The immune system, composed of white blood cells, provides the major line of defense against infectious microorganisms. Plasma cells are white blood cells that secrete proteins called antibodies. These antibodies normally circulate throughout the body, looking for infectious organisms. The antibodies attach to the microorganisms and promote their destruction.
However, in some individuals, too many antibodies are produced, and many of them can "go bad" in that they attach to normal tissues rather than the foreign invaders. These antibodies are referred to as autoantibodies, and they are thought to promote many forms of autoimmune diseases, including lupus, rheumatoid arthritis, myasthenia gravis, immune thrombocytopenic purpura (ITP) and autoimmune thyroiditis, to name a few. So, Dr. Roopenian and his colleagues sought to devise methods to reduce the number of autoantibodies available for tissue destruction.
The research team focused on FcRn, whose normal job is to preserve antibodies in the circulation. "While a good thing in normal individuals, FcRn could be working too efficiently in patients with lupus and rheumatoid arthritis," explains Dr. Roopenian. "The consequence is the maintenance of dangerously high levels of autoantibodies."
To test this idea, Dr. Roopenian used mice that normally develop arthritis caused by autoantibodies. His team shows that the elimination or blocking of FcRn resulted in the reduction of autoantibodies and a corresponding protection from arthritis. "These findings suggest FcRn is a potential therapeutic target for many forms of autoimmune disease caused by antibodies," he says.
Journal
Journal of Clinical Investigation