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.
Erin Digitale | EurekAlert!
Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn
New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences