Featured Research

from universities, journals, and other organizations

Immune System 'Atlas' Will Speed Detection Of Kidney Transplant

Date:
February 28, 2009
Source:
Stanford University Medical Center
Summary:
Scientists have devised a new way to decode the immune signals that cause slow, chronic rejection of all transplanted kidneys.

Scientists at the Stanford University School of Medicine and Lucile Packard Children's Hospital have devised a new way to decode the immune signals that cause slow, chronic rejection of all transplanted kidneys. They've created an immune-system "atlas" that will improve doctors' ability to monitor transplanted organs and shed light on the mechanisms of gradual, cumulative kidney malfunction after transplant.

"The reason chronic injury occurs in transplanted organs is really a mystery," said senior study author Minnie Sarwal, MD, PhD, professor of pediatrics at the School of Medicine and a nephrologist at Packard Children's Hospital. "Even patients who receive an organ from an identical twin develop chronic rejection."

The findings will be published online Feb. 23 in the Proceedings of the National Academy of Sciences.

Before an organ transplant, doctors check for compatibility between the donor's and recipient's immune systems, Sarwal said. They examine the genes encoding small proteins, called human leukocyte antigens, that label the exterior of every cell. These proteins are the immune system's main mechanism for distinguishing "self" from "non-self" tissues. Only identical twins have perfectly matched human leukocyte antigens; for other organ recipients, doctors use a donor with the closest match they can find. After transplant, an organ recipient receives strong drugs that reduce the body's ability to crank out antibodies — immune "search-and-destroy" markers — against the donated kidney.

But the fact that chronic organ rejection occurs even between twins suggests the immune system is doing more than keeping tabs on human leukocyte antigens.

The Stanford team set out to find what that was. The researchers devised a first-of-its-kind method to catalog every one of the antibodies attacking donated kidneys after transplant. They tracked evidence of all types of immune system attack by comprehensively comparing antibody levels in 18 kidney recipients before and after transplant. To do this, they melded two biological sleuthing systems, first comparing all proteins in the subjects' blood to an array of more than 5,000 human proteins, then running the results from that analysis through a genetic database that showed which blood proteins were antibodies designed to attack the donated kidney.

"This is pretty revolutionary," Sarwal said. "It opens the door to a lot of exciting work to personalize how we monitor these patients." The new findings will allow inexpensive, noninvasive blood tests that show whether a donated kidney is infected, undergoing acute rejection or accruing chronic injuries that could cause long-term malfunction, she said.

"An individual's antibody profile is a new aspect of human physiology that can now be surveyed in an unbiased way, the same way genes can," said co-senior author Atul Butte, MD, PhD, assistant professor of medical informatics and of pediatrics. "That's very exciting." Butte is also a member of the Stanford Cancer Center. Unlike genes, the body's antibodies change over time, a factor that could improve the effectiveness of personalized medicine, Butte said.

The team's raw data on antibody profiles is now publicly available to other scientists through the Gene Expression Omnibus database maintained by the National Center for Biotechnology Information, a division of the National Library of Medicine.

In addition to improving patient monitoring, the team's comprehensive list of anti-kidney antibodies will spur research on the mechanisms of chronic kidney rejection. For example, the study establishes for the first time what part of the kidney causes the largest immune response after transplant.

"To our great surprise, the most immunogenic region of the kidney is the renal pelvis," Sarwal said. The renal pelvis is the cavity deep inside the organ that collects urine and funnels it toward the bladder. The next-largest immune responses were observed at the cortex and glomerulus, regions of the kidney with large blood supplies and extensive exposure to the recipient's immune system. The next step in understanding chronic organ rejection will be to identify which specific anti-kidney antibodies are the most reliable harbingers of renal malfunction, Sarwal said.

"If we can correlate these antibodies with clinical events in the organ, we'll have the tools to extend the life of kidney transplants," Sarwal concluded.

Other Stanford co-authors include Li Li, senior biostatistician in pediatric nephrology; Persis Wadia, PhD, postdoctoral scholar; Rong Chen, PhD, research software engineer; Neeraja Kambham, MD, associate professor of pathology; Maarten Naesens, PhD, visiting research scholar in pediatric nephrology; Tara Sigdel, PhD, postdoctoral scholar in pediatrics; and David Miklos, MD, PhD, assistant professor of blood and marrow transplantation and a member of the Stanford Cancer Center. The research was funded by grants from the National Institute of Allergy and Infectious Disease and the National Library of Medicine.


Story Source:

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


Journal Reference:

  1. Li et al. Identifying compartment-specific non-HLA targets after renal transplantation by integrating transcriptome and "antibodyome" measures. Proceedings of the National Academy of Sciences, 2009; DOI: 10.1073/pnas.0900563106

Cite This Page:

Stanford University Medical Center. "Immune System 'Atlas' Will Speed Detection Of Kidney Transplant." ScienceDaily. ScienceDaily, 28 February 2009. <www.sciencedaily.com/releases/2009/02/090223221330.htm>.
Stanford University Medical Center. (2009, February 28). Immune System 'Atlas' Will Speed Detection Of Kidney Transplant. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2009/02/090223221330.htm
Stanford University Medical Center. "Immune System 'Atlas' Will Speed Detection Of Kidney Transplant." ScienceDaily. www.sciencedaily.com/releases/2009/02/090223221330.htm (accessed July 31, 2014).

Share This




More Health & Medicine News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Dangerous Bacteria Kills One in Florida

Dangerous Bacteria Kills One in Florida

AP (July 31, 2014) Sarasota County, Florida health officials have issued a warning against eating raw oysters and exposing open wounds to coastal and inland waters after a dangerous bacteria killed one person and made another sick. (July 31) Video provided by AP
Powered by NewsLook.com
Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Peace Corps Pulls Workers From W. Africa Over Ebola Fears

Peace Corps Pulls Workers From W. Africa Over Ebola Fears

Newsy (July 30, 2014) The Peace Corps is one of several U.S.-based organizations to pull workers out of West Africa because of the Ebola outbreak. Video provided by Newsy
Powered by NewsLook.com
Weather Kills 2K A Year, But Storms Aren't The Main Offender

Weather Kills 2K A Year, But Storms Aren't The Main Offender

Newsy (July 30, 2014) Health officials say 2,000 deaths occur each year in the U.S. due to weather, but it's excessive heat and cold that claim the most lives. Video provided by Newsy
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