Newer Rheumatoid Arthritis Drugs Lower Production of B Cells

FRIDAY Jan. 25, 2008 -- Certain drugs used to treat rheumatoid arthritis (RA) provide a powerful, previously unknown, benefit for the immune system, say University of Rochester Medical Center researchers.

They found that drugs known as anti-TNF compounds -- including Enbrel, Humira and Remicade -- help reduce the activity of abnormal B cells that play a role in autoimmune diseases such as RA and lupus. TNF is a chemical messenger that fires up the immune system. Anti-TNF drugs inhibit TNF.

The findings, published in the Jan. 15 issue of The Journal of Immunology, suggest that these drugs improve the health of patients in a way that hadn't been recognized, the researchers said.

"The most important considerations for any drug are: Is it safe, and does it work? 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 been treated with these medications, we really haven't understood to a significant degree how they actually work," research co-leader Dr. Ignacio Sanz, a professor of medicine, microbiology and immunology, said in a prepared statement.

Sanz and his colleagues studied 45 adults with RA and 22 healthy adults. Some of the RA patients received the anti-TNF medication etanercept (Enbrel), some received an older medication called methotrexate, and others received both drugs.

Among patients who took etanercept, there was a 40 percent drop in the percentage of B cells in lymph tissue. The RA patients who took etanercept also had about 75 percent fewer germinal centers, and the germinal centers that did exist in these patients were smaller and less organized than those in patients who didn't receive anti-TNF therapy.

Germinal centers are structures in the lymph system that appear when people have infections. These centers produce B cells, which the body uses to mark invaders for destruction. In healthy people, germinal centers fade away after recovery from an infection. But in people with RA and other chronic autoimmune diseases, germinal centers remain active.

"This is a critical piece of the immune system. 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," study co-leader Dr. Jennifer Anolik, an assistant professor of medicine, said in a prepared statement.

Anti-TNF drugs appear to disrupt the formation of special cells (follicular dendritic cells) that link germinal centers, which decreases the number of abnormal B cells, Anolik said.

"There is a lot of excitement about the role of B cells in autoimmune disease. The connection between TNF-targeted therapy and B cells in rheumatoid arthritis really hasn't been appreciated," she said.

Anolik is about to launch a study to compare how two different anti-TNF drugs affect B cells in RA patients. The findings could help explain why some RA patients respond well to certain drugs but not others.

More information

The U.S. National Institute of Allergy and Infectious Diseases has more about autoimmune disorders.

Posted: January 2008


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