Apr 10, 2002
By Merritt McKinney
NEW YORK, (Reuters Health)
In a finding that suggests a new approach for treating autoimmune diseases, researchers have uncovered the mechanism by which immune cells sometimes turn against the body's own cells.
The next step is "to learn more about this activation pathway so that we will be able to turn it off," the study's lead author, Dr. Ann Marshak-Rothstein of Boston University in Massachusetts, told Reuters Health.
Marshak-Rothstein explained in an interview that under normal circumstances, white blood cells called B cells have surface receptors that allow them to recognize proteins called antigens on foreign cells. When a receptor recognizes a foreign antigen, it triggers the formation of antibodies to attack outside invaders. Another set of receptors on B cells are capable of recognizing antigens on the body's own tissue, but they rarely do so, according to Marshak-Rothstein.
In certain autoimmune diseases such as multiple sclerosis, lupus and rheumatoid arthritis, however, the immune system turns against the body's own tissue. Marshak-Rothstein noted that the normally dormant B-cell receptors that recognize self-antigens become activated and trigger the production of so-called autoantibodies that attack the body's own cells.
"Exactly how that process gets started has been uncertain," she said.
Now Marshak-Rothstein and her colleagues report that the receptors for self-antigens interact with another receptor to trigger the formation of autoantibodies. The findings are published in the April 11th issue of the journal Nature.
Marshak-Rothstein explained that receptors for self-antigens do not bind very strongly to the antigens. Her team found that the autoantibody production process begins only after the receptor for self-antigen carries the antigen into another part of the cell to bind with a receptor called TLR9.
This pathway is "an excellent target" for medications to prevent an autoimmune reaction, Marshak-Rothstein said, since it "has nothing to do with" normal immune reactions. She noted that a common antimalarial drug called chloroquine, which is used to treat some autoimmune diseases, blocks TLR9.
Now that researchers understand why chloroquine benefits people with autoimmune diseases, Marshak-Rothstein said, "we should be able to design better drugs" that do not have as many side effects.
The report is "a major leap forward in understanding what drives autoimmune diseases such as rheumatoid arthritis and systemic lupus," Dr. Christopher C. Goodnow, of the Australian National University in Canberra, told Reuters Health.
The researchers have identified "a biochemical pathway for targeting new drugs to treat these diseases," according to Goodnow, who is the co-author, along with a colleague, Dr. Carola G. Vinuesa, of a related editorial.
SOURCE: Nature 2002;416:595-598, 603-607.
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