Featured Research

from universities, journals, and other organizations

Experimental Procedure Induces Tolerance To Mismatched Kidney Transplants

Date:
January 24, 2008
Source:
Massachusetts General Hospital
Summary:
Four of five patients participating in a trial of an experimental protocol designed to induce immune tolerance to HLA-mismatched kidney transplants have been able to discontinue immunosuppressive drugs. The report describes the first successful, intentional induction of tolerance across the HLA barrier in a group of transplant recipients. Combined organ and bone marrow transplant allows patients to halt immunosuppression.

Four of five patients participating in a trial of an experimental protocol designed to induce immune tolerance to HLA-mismatched kidney transplants have been able to discontinue immunosuppressive drugs. A mismatch of HLA (human leukocyte antigen) proteins is the most difficult immunological barrier to transplantation.

"We are very encouraged by our initial success in inducing tolerance across the HLA barrier, something that has been a major goal of transplant immunology for years," says David H. Sachs, MD, director of the MGH Transplantation Biology Research Center, the study's senior author.* "While we need to study this approach in a larger group of patients before it is ready for broad clinical use, this is the first time that tolerance to a series of mismatched transplants has been intentionally and successfully induced."

For more than three decades, Sachs and his colleagues have been pursuing ways to induce tolerance, tricking the immune system into regarding a donor organ as "self." Over the years the team has developed an approach in which the organ recipient receives bone marrow from the donor along with the needed organ to produce a state called mixed chimerism, an immune system that blends elements of both the donor and recipient.

In 1998 the team first used this approach in a woman whose kidney failure had been caused by the bone marrow cancer multiple myeloma, which can be treated with marrow transplantation. That patient received both marrow and a kidney from her HLA-matched sister and was able to discontinue immunosuppressive drugs about two months later. More than nine years later she remains healthy, and since then six more patients with myeloma-induced kidney failure have successfully become tolerant to HLA-matched transplants through this process

The current study enrolled five patients whose kidney failure resulted from non-cancerous conditions and who did not have an HLA-matched living donor. The study protocol begins with therapy designed to partially destroy the recipient's bone marrow and treatment with an antibody that reduces the level of T cells, the immune system component primarily involved in organ rejection. After receiving the transplanted kidney and bone marrow, patients stay in a relatively sterile environment for about two weeks, allowing the bone marrow to regenerate and produce new immune cells that are tolerant of the donor organ.

The first two patients in the trial were successfully weaned from immunosuppressive drugs in the months following their transplant, but the third patient developed early rejection and eventual failure of the donor kidney. Since the antidonor immune response of that patient -- who subsequently received a successful second transplant with conventional immunosuppression -- was primarily caused by the immune system's B cells, the study protocol was adjusted to include an additional antibody targeting B cells. The fourth and fifth patients, both of whom received the revised protocol, were able to discontinue immunosuppressives 8 and 10 months after their tranplants. All four of the successfully transplanted patients continue to have normal kidney function from two to more than five years later.

As seen in previous animal studies and in some of the myeloma patients receiving matched transplants, the chimeric state -- the presence in bone marrow of immune cells from both recipient and donor -- was temporary, even though tolerance to donor tissue continues. Sachs and his colleagues are continuing to investigate this phenomenon, which they believe may involve some factor provided by the donor organ. "We have shown in monkeys that the kidney itself is required to maintain this state that we call peripheral tolerance, although we still don't fully understand the mechanism," he explains.

*The report of the study conducted at Massachusetts General Hospital (MGH) appears in the January 24 New England Journal of Medicine.

The study was supported by grants from the Immune Tolerance Network; the National Institute of Allergy and Infectious Diseases; the National Institute of Diabetes, Digestive and Kidney Diseases; and the Juvenile Diabetes Research Foundation. Additional co-authors of the NEJM report are Susan Saidman, PhD, Juanita Shaffer, Frederic Preffer, PhD, Jay Fishman, MD, Bimalangshu Dey, MD, Dicken Ko, MD, Martin Hertl, MD, Nelson Goes, MD, Waichi Wong, MD, Winfrid Williams, and Robert Colvin, MD, of the MGH; and Manikkam Suthanthiram, MD, Ruchuang Ding, MD, and Vijay Sharma, PhD, Weill Medical College of Columbia University.


Story Source:

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


Cite This Page:

Massachusetts General Hospital. "Experimental Procedure Induces Tolerance To Mismatched Kidney Transplants." ScienceDaily. ScienceDaily, 24 January 2008. <www.sciencedaily.com/releases/2008/01/080123173157.htm>.
Massachusetts General Hospital. (2008, January 24). Experimental Procedure Induces Tolerance To Mismatched Kidney Transplants. ScienceDaily. Retrieved September 22, 2014 from www.sciencedaily.com/releases/2008/01/080123173157.htm
Massachusetts General Hospital. "Experimental Procedure Induces Tolerance To Mismatched Kidney Transplants." ScienceDaily. www.sciencedaily.com/releases/2008/01/080123173157.htm (accessed September 22, 2014).

Share This



More Health & Medicine News

Monday, September 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Liberia Pleads for Help to Fight Ebola

Liberia Pleads for Help to Fight Ebola

AP (Sep. 22, 2014) Liberia's finance minister is urging the international community to quickly follow through on pledges of cash to battle Ebola. Bodies are piling up in the capital Monrovia as the nation awaits more help. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Ebola Doctor Says Border Controls Critical

Ebola Doctor Says Border Controls Critical

AP (Sep. 22, 2014) A Florida doctor who helped fight the expanding Ebola outbreak in West Africa says the disease can be stopped, but only if nations quickly step up their response and make border control a priority. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Global Ebola Aid Increasing But Critics Say It's Late

Global Ebola Aid Increasing But Critics Say It's Late

Newsy (Sep. 21, 2014) More than 100 tons of medical supplies were sent to West Africa on Saturday, but aid workers say the global response is still sluggish. Video provided by Newsy
Powered by NewsLook.com
Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
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:
from the past week

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