UT Southwestern researchers probe kidney damage, protectio...( DALLAS April 21 2009 Kidney damage...)

DALLAS April 21, 2009 Kidney damage associated with the autoimmune disease lupus is linked to a malfunction of immune cells that causes them to congregate in and attack the organs, researchers at UT Southwestern Medical Center have discovered in a mouse study.

In a separate study with an international team, the researchers also found that a certain set of genes appears to protect the kidneys from a different sort of immune attack in both mice and humans.

"These studies, taken together, uncover two important molecules that underlie the pathology of lupus, particularly kidney disease," said Dr. Edward Wakeland, chairman of immunology at UT Southwestern and co-senior author of the studies.

"In addition, they highlight a certain molecule as a potential target for treating this disease," he said.

In the first study, which appears in the April issue of The Journal of Immunology, the researchers examined several strains of mice that mimic human lupus. They found that immune cells in those mice overproduced a particular molecule called CXCR4. In fact, the mice had up to twice as much CXCR4 as their normal counterparts in several types of immune cells. The lupus-prone mice also had more immune-system cells in their kidneys, indicating that the inflammatory action of the immune cells might be causing the kidney damage.

The CXCR4 molecule was already known to play a role in creating various types of blood cells and also has been shown to be active in cancer and AIDS. Cells with CXCR4 on their surface are attracted to another molecule released by cells in various organs, so they migrate toward those organs, including the kidney.

When the researchers treated the lupus mice with a substance that blocks CXCR4, the symptoms of lupus significantly diminished; many symptoms of kidney failure were averted; and the mice lived longer. The increased lifespan was greater when treatment began at an early age.