Description of HLA
HLA stands for “Human Leukocyte Antigen.” These antigens are protein molecules we inherit from our parents. Together, these molecules make up your HLA type. We currently know about more than 2500 different HLA molecules. It is very important to determine your HLA type before you have a stem cell transplant, and we can do this by taking a sample of your blood or other body tissue cells.
HLA testing will also determine the HLA type of anyone who may donate stem cells to you. It is important in stem cell transplants to see how closely the HLA type of the transplant patient matches the HLA type of the stem cell donor. The HLA “match” is the number of HLA molecules that any two people have in common for stem cell transplantation. HLA matching is usually based on 10 HLA molecules. The more molecules two people share, the better the match. When two individuals share the same HLA molecules, they are said to be a good “match.” That is, their immune systems will not see each other as “foreign” and are less likely to attack each other.
The most likely place to find an HLA match between two people is among siblings (that is, brothers and sisters who have the same mother and same father). If two siblings inherit the very same HLA molecules from both parents, they are said to be an “HLA identical match.”
You have a 25 percent (1 in 4) chance of being an HLA identical match with your sibling. Why? Because there is a basic rule in HLA inheritance: you have a 25 percent chance of inheriting the same HLA molecules as your sibling, a 25 percent chance of inheriting none of the same HLA molecules as your sibling, and a 50 percent chance of inheriting half of the same HLA molecules as your sibling.
However, two unrelated people can just happen to be a good HLA match, too. Although it is less likely, it is possible that you could have some of the same HLA molecules as someone you don’t even know.
Finding the Best Match
When a doctor decides that a stem cell transplant is the best treatment for a patient, the patient, all of his or her siblings, and sometimes their parents will have samples collected for HLA typing. If one of the family members is an HLA identical match, the lab will do further testing to be absolutely sure that they are the best match possible.
If none of the siblings are a good HLA match, the doctor will sometimes ask to have additional family members tested. Since your HLA type is inherited from your parents and passed on to your children, among your relatives, your parents and children have the next best chance of being closely HLA matched with you. If it happens that there are no close HLA matches within the patient’s family, an unrelated search can be initiated in order to find an unrelated volunteer donor with the same HLA molecules as the patient.
What Are HLA Antibodies?
HLA antibodies are proteins that may be present in the patient’s blood, which could interfere with the success of the transplant. If the stem cell donor is not an absolutely perfect match, HLA antibodies can attack the donated stem cells and may make the patient’s body reject them. The patient may also need to have transfusions of platelets during the recovery period. HLA antibodies can interfere with platelet transfusions by killing the donated platelets before they have a chance to work. That is why patients are tested for HLA antibodies before a transplant.
Some people do not develop HLA antibodies at all, while others do. It is not clearly understood why this is so, but people are most likely to develop HLA antibodies from pregnancies, prior blood or platelet transfusions, or organ transplants.
The HLA antibody level is referred to as the PRA (Panel Reactive Antibody). The PRA tells us what percentage of the general population the patient has HLA antibodies to, and can give us a good idea about how easy or difficult it will be to find a compatible platelet donor for this patient. In addition to measuring how much or how little PRA a patient has, we can also test if a patient has antibody to a particular HLA molecule. Some patients have antibody to one or two HLA molecules, while others have antibodies to many HLA molecules and therefore have a higher PRA.
HLA: Human Leukocyte Antigen, proteins we inherit from our parents, found on the surface of cells, also called histocompatibility or tissue antigens.
HLA Matching: Comparing the number of HLA molecules (antigens) two people have in common.
Haplotype: a set of HLA antigens that are inherited from each parent.
Molecular HLA typing: an HLA typing that was determined by using DNA to look at the gene that codes for the protein found on the surface of the cells.
Serologic HLA typing: an HLA typing that was determined by looking at the reactivity of the HLA molecule on the surface of the cells with known antibodies.
HLA Antibodies: proteins in the patient’s blood directed against the donor’s HLA that could attack transplanted or transfused cells.
PRA: Panel Reactive Antibody: a measure of how much HLA antibody the patient has.
Crossmatch: a laboratory test that looks for patient antibodies directed against a potential donor’s cells.
Stem Cell: cells responsible for generating red blood cells, white blood cells, and platelets.
Bone Marrow: the inner spongy portion of large bones, where most stem cells reside.
Graft versus Host Disease (GVHD): an immune attack by transplanted donor cells against the patient’s body.
Host versus Graft (HVG): an immune attack by the patient’s cells (host) against the donated (transplanted) cells (graft), can lead to the patient's rejection of the transplant.
The Science Behind HLA Typing