Pathway Kicks Off Autoimmune Response

[Guest guest]

Pathway Kicks Off Autoimmune Response

Wed Apr 10, 5:23 PM ET

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.

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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[Guest guest]

wow i hope this is true and they can find better ways to help us soon. kathy

in il