Featured Research

from universities, journals, and other organizations

Rockefeller University Researchers Find New Pathway For Kidney Disease In Lupus

Date:
February 19, 1998
Source:
Rockefeller University
Summary:
Studies on mice with a disease similar to systemic lupus erythematosus, a devastating autoimmune disease that causes chronic inflammation and severe kidney disease, point to a novel therapeutic approach to treating this disease in humans, report scientists from The Rockefeller University in the Feb. 13 Science. These findings force a rethinking of the current scientific literature on this disease, according to the researchers.

Studies on mice with a disease similar to systemic lupus erythematosus, a devastating autoimmune disease that causes chronic inflammation and severe kidney disease, point to a novel therapeutic approach to treating this disease in humans, report scientists from The Rockefeller University in the Feb. 13 Science. These findings force a rethinking of the current scientific literature on this disease, according to the researchers.

Systemic lupus erythematosus affects mostly women between the ages of 20 and 40. The disease develops when the immune system, which normally attacks foreign invaders such as viruses and bacteria, attacks the body's own tissues. The immune system produces antibodies, called autoantibodies, directed against its own cells. Physicians generally prescribe antiinflammatory and immune system-suppressing drugs to treat the disease. These drugs, in addition to causing unwanted side-effects, are generally ineffective and non-specific. The new research identifies a critical link between autoantibodies and inflammation and suggests novel ways of uncoupling this connection.

"These studies show that preventing the activation of antibody receptors by autoantibodies is an effective way to treat autoimmune diseases like lupus," says senior author Jeffrey V. Ravetch, M.D., Ph.D., Theresa and Eugene Lang Professor and head of the Leonard Wagner Laboratory of Molecular Genetics and Immunology.

Prior to these studies the current dogma on how autoantibodies caused disease in lupus was based on a component of the immune system called the complement system, which comprises about 25 molecules that work in concert to aid in destroying bacteria. Complement was also thought to trigger inflammation caused by antibody-coated antigens, called immune complexes, which circulate through the bloodstream and are deposited in various tissues and organs in autoimmune diseases. Complement proteins, which can cause blood vessels to become dilated and leaky, contribute to the redness, warmth, swelling, pain and loss of function that characterize an inflammatory response.

Research from the Ravetch lab and elsewhere during the last few years has pointed to an alternative pathway in the immune system reaction in autoimmune diseases like lupus. In this approach, scientists think that Fc receptors, antibody-binding molecules that are crucial to both triggering an immune response and to turning off the response once the threat has been eliminated, play an important role. The role of complement in this pathway appears to be minimal.

In the new research, Ravetch and co-authors Raphael Clynes, M.D., Ph.D., and Calin Dumitru, developed a strain of mice lacking the gamma chain of the Fc receptor, which is responsible for activating immune cells by antibody complexes. When these Fc receptor deficient mice were bred to a strain of mice that spontaneously develop a disease closely matching human lupus, the researchers found a striking difference in the survival rates between mice missing the Fc receptor and those with an intact receptor. Eighty-two percent of mice without the Fc receptor were alive after nine months, as compared to less than 20 percent for lupus mice with an intact Fc receptor.

Ravetch and his colleagues found evidence of immune complexes and a complement protein called C3 in the kidneys of both strains of mice, but the Fc receptor deficient mice showed no evidence of inflammatory disease.

"These results show that despite the presence of immune complexes and C3 in the kidney, the inflammatory response is uncoupled, indicating that Fc gamma receptors are required for the initiation of the inflammatory cascade and complement activation is not sufficient," says Ravetch. "These findings argue for the development of new therapeutic strategies for the treatment of lupus based on blocking Fc receptors."

This work was supported by the National Institute of Allergy and Infectious Diseases and the National Institute of Diabetes and Digestive and Kidney Diseases, both part of the federal government's National Institutes of Health.

Rockefeller began in 1901 as The Rockefeller Institute for Medical Research, the first U.S. biomedical research center. Rockefeller faculty members have made significant achievements, including the discovery that DNA is the carrier of genetic information and the launching of the scientific field of modern cell biology. The university has ties to 19 Nobel laureates, including the president, Torsten N. Wiesel, M.D., who received the prize in 1981. The university recently created six centers to foster collaborations among scientists to pursue investigations of Alzheimer's disease, of biochemistry and structural biology, of human genetics, of immunology and immune diseases, of sensory neurosciences and of the links between physics and biology.


Story Source:

The above story is based on materials provided by Rockefeller University. Note: Materials may be edited for content and length.


Cite This Page:

Rockefeller University. "Rockefeller University Researchers Find New Pathway For Kidney Disease In Lupus." ScienceDaily. ScienceDaily, 19 February 1998. <www.sciencedaily.com/releases/1998/02/980219061622.htm>.
Rockefeller University. (1998, February 19). Rockefeller University Researchers Find New Pathway For Kidney Disease In Lupus. ScienceDaily. Retrieved October 23, 2014 from www.sciencedaily.com/releases/1998/02/980219061622.htm
Rockefeller University. "Rockefeller University Researchers Find New Pathway For Kidney Disease In Lupus." ScienceDaily. www.sciencedaily.com/releases/1998/02/980219061622.htm (accessed October 23, 2014).

Share This



More Health & Medicine News

Thursday, October 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Working Mother (Oct. 22, 2014) Is your child ready? Video provided by Working Mother
Powered by NewsLook.com
U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

Newsy (Oct. 22, 2014) Now that the U.S. is restricting travel from West Africa, some are dropping questions about a travel ban and instead asking about visa bans. Video provided by Newsy
Powered by NewsLook.com
US to Track Everyone Coming from Ebola Nations

US to Track Everyone Coming from Ebola Nations

AP (Oct. 22, 2014) Stepping up their vigilance against Ebola, federal authorities said Wednesday that everyone traveling into the US from Ebola-stricken nations will be monitored for symptoms for 21 days. (Oct. 22) Video provided by AP
Powered by NewsLook.com
Doctors Help Paralysed Man Walk Again, Patient in Disbelief

Doctors Help Paralysed Man Walk Again, Patient in Disbelief

AFP (Oct. 22, 2014) Polish doctors describe how they helped a paralysed man walk again, with the patient in disbelief at the return of sensation to his legs. Duration: 1:04 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins