They do this, researchers say, by breaking up so−called molecular "training camps" for rogue cells that play a key role in autoimmune diseases.
Physicians and scientists at the University of Rochester Medical Center reports the discovery that drugs known as anti−TNF compounds − Enbrel, Humira, Remicade and others — have a positive effect on B cells, which are involved in many autoimmune diseases such as rheumatoid arthritis and lupus.In most people, once an infection is beaten off, the germinal centers close down. But in people with a chronic autoimmune disease...germinal centers stick around...
The team found that anti−TNF compounds help eliminate abnormal B cell activity, raising the possibility that the drugs could improve the health of those with autoimmune disease in ways that no one has foreseen.
They studied the immune system in a way rarely done in people, working with ear, nose and throat doctors who took a small snip from a subject's tonsils, which enabled them to look directly at the activity of the immune system, rather than inferring its activity based on cells in the blood.
It turned out that anti−TNF drugs disrupt structures in our lymph system's germinal centers, which are a type of training camp for immune cells. Normally, the structures appear when we are sick, swiftly churning out lots of B cells, which the body uses to mark infectious agents and other invaders for destruction.
In healthy people, once an infection is beaten off, the germinal centers close down. But in people with a chronic autoimmune disease such as rheumatoid arthritis or lupus, germinal centers stick around too long, training an army of immune cells that, in the absence of a real enemy, wreak havoc throughout the body by mistakenly attacking our own tissues.
"This is a critical piece of the immune response," said one researcher. "Germinal centers are where crucial education of the B cell takes place − where they learn which cells to attack and which ones not to. Dysregulation in germinal center reactions may play a role in many autoimmune diseases."
Published in the January 15, 2008 issue of the Journal of Immunology, the study included 45 patients with rheumatoid arthritis and 22 healthy adults. Some of the patients with arthritis received etanercept (Enbrel); others received an older medication, methotrexate; and others received both.
In their study, the team found that the anti−TNF medication dropped the percentage of memory B cells in the lymph tissue by about 40 percent in patients. They also found that arthritis sufferers who received anti−TNF therapy had about one−quarter the number of germinal centers as other arthritis patients. The germinal centers that did exist were smaller and less organized.
"The most important considerations for any drug are: Is it safe, and does it work?" said Ignacio Sanz, M.D., professor of Medicine, Microbiology and Immunology. "The answer is certainly 'yes' to both questions for these anti−TNF compounds. The drugs have revolutionized the treatment of patients with rheumatoid arthritis. But it also turns out that, even though millions of patients have been treated with these medications, we really haven't understood to a significant degree how they actually work."
