Unexpected variation in immune genes poses difficulties for transplantation

August 3, 2012

the genes that allow our immune system to tell the difference between our own cells and foreign invaders – are evolving much more rapidly than previously thought, according to an article online on August 3 in Trends in Genetics. The resulting degree of variation improves our ability to fight off disease, but could also present challenges to current worldwide efforts aimed at identifying potential donors for patients undergoing stem cell transplantation.

"This new work makes clear the daunting and near hopeless challenge of keeping track of the continuous output from the HLA mutational spigot," says first author William Klitz, from the University of California, Berkeley.

HLA proteins sit at the surface of human cells. Every individual has a specific HLA on the surface of their cells and these proteins effectively act as an identification card. Any other that have the same HLA on the outside are recognized as 'self'; foreign particles like bacteria or viruses are identified as invaders and the kicks in to remove them. The same system that helps us fight off germs makes organ or stem cell transplantation difficult. Our bodies treat transplanted tissue as foreign and reject it. Unless, however, the patient and the donor share the same HLA . As a result, worldwide efforts are underway to identify all possible HLA variants, in the hopes of more effectively matching patients with potential donors.

The difficulty is that within the human population, HLA genes are mutating rapidly and Klitz estimates that more than a million variants exist in the current population. Trying to identify all the variants will be nearly impossible and ultimately pointless, according to Klitz, because of how quickly these genes are evolving. This rapid evolution is a boon in some ways because it means that, at the population level, our immune systems are getting better at fighting off pathogens. For transplant recipients, however, the most likely implication is that the best chance for a match will be found in first-degree relatives rather than in a worldwide search for donors.

Explore further: Transplant survival could be improved by altering present criteria for matching donors, recipients

More information: Klitz et al.: "New reservoirs of HLA alleles: Pools of rare variants enhance immune defense" Trends in Genetics, 2012.

Related Stories

Transplant survival could be improved by altering present criteria for matching donors, recipients

October 6, 2011
Selecting better matched recipients and donors than is currently required for umbilical-cord blood transplantation could substantially reduce transplant-related deaths. The findings, published Online First in the Lancet Oncology ...

Elimination of national kidney allocation policy improves minority access to transplants

July 21, 2011
A new study published in the American Journal of Transplantation reveals that since the elimination of the kidney allocation priority for matching for HLA-B on May 7, 2003, access to kidney transplantation for minorities ...

Study examines factors in pediatric kidney transplant rejection

July 18, 2011
Avoiding HLA-DR mismatching appears to be beneficial in pediatric kidney transplant patients, however the likelihood of finding a matching donor must be considered against the wait time for a possible donation, according ...

Recommended for you

Australian researchers in peanut allergy breakthrough

August 17, 2017
Australian researchers have reported a major breakthrough in the relief of deadly peanut allergy with the discovery of a long-lasting treatment they say offers hope that a cure will soon be possible.

Genetic variants found to play key role in human immune system

August 16, 2017
It is widely recognized that people respond differently to infections. This can partially be explained by genetics, shows a new study published today in Nature Communications by an international collaboration of researchers ...

Study identifies a new way to prevent a deadly fungal infection spreading to the brain

August 16, 2017
Research led by the University of Birmingham has discovered a way to stop a deadly fungus from 'hijacking' the body's immune system and spreading to the brain.

Biophysics explains how immune cells kill bacteria

August 16, 2017
(Tokyo, August 16) A new data analysis technique, moving subtrajectory analysis, designed by researchers at Tokyo Institute of Technology, defines the dynamics and kinetics of key molecules in the immune response to an infection. ...

How a nutrient, glutamine, can control gene programs in cells

August 15, 2017
The 200 different types of cells in the body all start with the same DNA genome. To differentiate into families of bone cells, muscle cells, blood cells, neurons and the rest, differing gene programs have to be turned on ...

Scientists identify gene that controls immune response to chronic viral infections

August 15, 2017
For nearly 20 years, Tatyana Golovkina, PhD, a microbiologist, geneticist and immunologist at the University of Chicago, has been working on a particularly thorny problem: Why are some people and animals able to fend off ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.