New Target for Lupus Treatment?
Key Chemical Signal Lets Lupus Immune Cells Hide in Spleen
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.