Health & Medical Immune System Disorders

New Target for Lupus Treatment?

New Target for Lupus Treatment?

New Target for Lupus Treatment?


Key Chemical Signal Lets Lupus Immune Cells Hide in Spleen

Sept. 14, 2006 -- An exciting new study shows a new target for future lupus treatments.

Lupus is an autoimmune disease: The body is attacked by its own immune system. In lupus, that attack may come from a kind of immune cell called a B cell.

As the body makes new B cells, a few of them go haywire and try to attack the body. Normally, the body quickly eliminates these cells. But in lupus, they somehow survive.

A special hormone called B-cell-activating factor -- or BAFF -- helps these self-attacking B cells survive. And people with lupus and some other autoimmune diseases overproduce BAFF. Eventually, these B cells build up to dangerous levels and cause lupus.

Hiding in the Spleen


Now a research team, including Michael Karin, PhD, of the University of California, San Diego, finds that B cells build up in a specific part of the spleen called the marginal zone. Mouse studies suggest that if the B cells can't hide in the spleen, they can't cause lupus.

What lets lupus-causing B cells lurk in the spleen is a chain of chemical signals called the NF-kB pathway. You need a functional NF-kB pathway for your immune system to fight infections. But this pathway is made up of two parts: the classical NF-kB pathway and the alternative NF-kB pathway.

In mouse experiments, Karin's team now finds that partial disruption of just the alternative NF-kB pathway is enough to keep lupus-causing B cells from hiding in the spleen.

"Our findings suggest that incomplete inhibition of the alternative NF-kB pathway ... may be a sufficient therapeutic option for patients suffering from autoimmune disease associated with BAFF overproduction," the researchers suggest. "Inhibition of the alternative NF-kB pathway is less likely to cause an immune deficiency, which is commonly seen after blockade of the classical NF-kB pathway."

The findings appear in the September issue of the journal Immunity.

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