Study Identifies New Treatment Target for Autoimmune Diseases

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Study Identifies New Treatment Target for Autoimmune Diseases

Results of a recent study supported in part by a grant from the

Alliance for Lupus Research (ALR) show that blocking the actions of a

protein called FcRn could help treat autoimmune diseases in which

autoantibodies play a key role, including systemic lupus

erythematosus (SLE, or lupus). Autoantibodies are antibodies that

target the body's own cells and tissues, contributing to inflammation

and tissue damage in lupus and other autoimmune diseases. ALR-funded

investigator Derry Roopenian, PhD, and his colleagues at the

Laboratory in Bar Harbor, ME, conducted the study on FcRn, which was

published in the May 1, 2004 issue of the Journal of Clinical

Investigation.

FcRn is normally responsible for extending the lifespan of a group of

antibodies in the blood known as IgG (immunoglobulin G) antibodies,

which play an important role in immunity. " Proteins in the blood have

a certain lifespan in the body, and usually disappear within 24

hours, " Dr. Roopenian explains. " FcRn preserves the IgG antibodies

from elimination, " allowing them to remain in the bloodstream for

much longer periods and help protect us against infections. But in

certain autoimmune diseases, including lupus and rheumatoid

arthritis, people produce way too many IgG antibodies, including

autoantibodies that attack normal tissues and contribute to disease.

To find out whether FcRn is involved in such diseases, Dr. Roopenian

and his colleagues used a mouse strain called K/BxN, which is

genetically programmed to develop a severe form of autoimmune

arthritis. The arthritis in these mice, which resembles rheumatoid

arthritis, is caused by IgG autoantibodies that trigger inflammation

and joint damage. The researchers found that eliminating the FcRn

protein through genetic engineering substantially reduced or slowed

the progression of arthritis in the K/BxN mice. Reduction of disease

was closely linked to a drop in the levels of IgG autoantibodies in

the blood. These findings indicate that FcRn is a critical component

of autoimmune diseases in which autoantibodies play a major role in

the disease process, and that it is a potential target for new

therapies that could block its function.

What it means for people with lupus

" There's a lot of overlap between lupus and arthritic diseases like

rheumatoid arthritis. Since autoantibodies contribute to both

diseases, FcRn is an attractive therapeutic target for their

treatment, " Dr. Roopenian says. As part of his ongoing ALR-funded

research,

Dr. Roopenian is now looking at mouse models of lupus (mice that

develop lupus-like disease) to see if they, too, are protected from

disease by a genetically engineered deficiency in FcRn. He and his

colleagues are also working to develop therapies that can block the

actions of FcRn. Treatments that selectively target FcRn are unlikely

to cause serious side effects like those caused by current lupus

drugs that suppress the entire immune system. Therapies that block

FcRn " are not going to be a cure-all, " Dr. Roopenian says, " but could

give you a cure when used in combination with other drugs under

development " that target other parts of the abnormal immune response

in lupus.