For patients battling a life-threatening illness, the hope of a cure through a blood stem cell or bone marrow transplant is a miracle. For that transplant to be successful, the patient and the donor must have a matching set of Human Leukocyte Antigens, or HLA. The HLA are markers on the surface of cells that help the immune system recognize which cells are “part of me” and which cells are “a threat”.
When a threat is found, the immune system mobilizes to eliminate the invading cells – whether a bacterial infection, a virus, or other pathogen. If the immune system were to see the cells from a transplant as “threat”, the transplant may not be successful, so finding the best possible HLA match is key to bone marrow and stem cell transplants. There is also a possibility for the transplanted cells to see the new host as “threat” and attack the recipient, a condition called Graft Versus Host Disease (GVHD). The closer the HLA match between a donor and recipient, the less likely the immune system will be triggered, and the more likely the transplant will have a positive result.
The chances of a match are highest within the immediate family but are not 100%. Statistically, 70% of patients must search the registries for a stranger who shares their HLA type, most often someone of the same genetic heritage or ethnicity.
Each of us inherits 50% of our HLA from our biological mother, and the other 50% from our biological father. The genes that determine HLA are split up when being passed down to a child, with a half-set coming from each parent to make a complete set for the child. There are four possible combinations of HLA from the parents. Each child has the same chance – 25% – of getting one of these four profiles in the genetic lottery when a human egg is fertilized. There is no way to predict which of the four combinations any given child will receive.
Which of the four possible HLA combinations you inherit from your parents is fairly random. You could get any one of these four combinations.
But what about your other siblings? Each one of them has the same 25% chance of inheriting any one of the four available HLA combinations. Every sibling has the same 25% chance of being your match. Since they could inherit one of two half-matched profiles, there are two 25% chances (or a 50% chance) that a sibling of yours is a half match. There is also a 25% chance for each sibling that they do not match you at all because they inherited the two HLA factors you did not get.
Identical twins share a nearly identical HLA profile since they both developed from a single fertilized egg. The first successful bone marrow transplant, completed in 1956, was between identical twins.
Fraternal twins, which develop from two separate zygotes, have the same 25% chance of matching each other as they do of matching their other siblings.
Half-siblings have a chance of being a half-match but cannot be a full match as they do not share both biological parents.
Because children inherit 50% of HLA from them, parents are each a half-match their children. It is rare for parents to donate to their own children, or vice versa, but in recent years, new drugs have made some half-matched transplants possible for certain patients.
We know that 70% of patients do not find a donor among their siblings, either due to the lack of a match, or some other factor, such as a matching sibling being unable to donate for health reasons. Fortunately, tens of millions of people around the world have volunteered as blood stem cell and bone marrow donors through registries like Gift of Life. Their HLA profiles are anonymously shared with an international database, so if a patient has a match overseas, they can be found and invited to donate.
Outside of the immediate family, the highest chance of finding a matching donor is with people who share the same genetic heritage or a similar ancestry. Since we inherit HLA types from our parents and ancestors, and these can be unique to geographic regions or ethnic groups, two people who share a similar ancestry are more likely to share HLA types. This means it is crucial that the registry become as diverse as possible, and Gift of Life urges everyone between 18 and 35 to please order a swab kit and join the registry.
Click here to read more about the urgent need to expand and diversify the registry.
Please contact us if you have questions about this article or need help with finding a matching donor.