Slowing lupus: Stifled inflammation limits kidney damage

Restoring the bodys balance between the actions of antibodies and natural regulatory proteins is the goal of a therapy being developed for the autoimmune disease lupus. This treatment thwarts activation of an array of immune-system proteins called complement, experiments in mice show. The findings clear the way for testing complement inhibition as a treatment for lupus patients.

Normally, antibodies bind to foreign targets such as bacteria and viruses. Complement proteins latch onto the antibodies, and the resulting immune complex destroys the invaders and creates debris in the bloodstream. Proteins called regulators of complement activation live up to their name by limiting how much complement joins the complexes, thereby fostering a healthy immune response.

In lupus, antibodies attack a persons own tissues, activating excess complement that gloms onto immune complexes. The resulting debris can overload housekeeper cells in the liver and spleen and settle in the kidneys, where it causes inflammation that jams blood flow and kills cells, says study coauthor Richard J. Quigg, a nephrologist at the University of Chicago. About half of lupus patients contract some kidney disease in their lifetimes, Quigg estimates.

To test whether complement suppression can slow lupus, Quigg and his colleagues used lupus-prone mice that were genetically engineered to produce excess amounts of a rodent regulator of complement activation. Mice overproducing this protein, called Crry, were about eight times as likely to survive at least 42 weeks as other lupus-prone mice were, the researchers found.

In another experiment on lupus-prone mice, 37 of 87 mice (42.5 percent) without extra Crry had kidney disease, but only 11 of 67 animals (16.4 percent) with extra Crry showed such damage.

The results will appear in an upcoming issue of the Journal of Immunology.

On the basis of this and other studies, researchers have started a trial in which lupus patients with kidney damage receive infusions of a complement inhibitor or an inert substance. The study is the first to use a complement inhibitor against lupus in people, says V. Michael Holers, a rheumatologist at the University of Colorado Health Sciences Center in Denver who coauthored the mouse study and is directing the study in lupus patients.

Giving complement inhibitor to people with lupus is plausible, potentially important, and increasingly supported by experimental data, says David Wofsy, a rheumatologist at the Veterans Affairs Medical Center in San Francisco.