Q: What is transplantation?
A: Transplantation is a procedure (or set of procedures) in which diseased and/or nonfunctioning organs, tissue or bone marrow is replaced with the same obtained from another healthy person. Transplants between identical twins will not be rejected because all the genes (antigens) are identical.
Q: What is histocompatibility?
A: “Histo” is a Greek word that means “tissue”. Histocompatibility refers to the quality or state of being histo or tissue compatible. This term is used in transplantation to describe the ability of a donor’s tissue or organ to be accepted by a recipient.
There is a group of genes present in all animals called the major histocompatibility complex (MHC). In humans the MHC is called human leukocyte antigen (HLA). The more HLA antigens shared between a recipient and donor, the better the potential outcome of the transplantation. For bone marrow transplantation, a near-perfect match is required whereas for kidney transplantation, a lesser match can result in a successful, functioning transplant.
Q: What is HLA?
A: Human Leukocyte Antigens are the human form of MHC and are proteins located on the surface of white blood cells and other tissues in the body. HLA antigens play an important role in the immune system’s defense against invaders such as bacteria, viruses and parasites.
In transplantation, when the donor’s HLA is different from the recipient’s, the immune system of the recipient will recognize the donor’s HLA antigens as foreign. This causes rejection of the transplanted tissue or organ.
Q: Why would a patient need HLA testing?
A: HLA typing is used to identify the best donor for a transplant recipient. In the best case scenario the donor will have the exact HLA antigens as the recipient. The risk of transplant rejection is lessened for well-matched donor-recipient pairs.
Certain diseases are associated with particular HLA types. For example, a person with ankylosing spondylitis (a disease like rheumatoid arthritis) is likely to have HLA-B27 antigens. HLA typing can help a physician differentiate ankylosing spondylitis from other disorders.
Q: How is a person’s HLA type determined?
A: HLA testing is performed on a sample of blood. An individual’s HLA typing can be determined by testing the HLA proteins on the surface of white blood cells or by testing DNA from the same cells.
Q: How is HLA typing performed?
A: HLA typing is performed in laboratories by trained technologists using blood drawn from a person’s arm. The blood can be separated into components such as red blood cells, white blood cells, platelets and plasma or serum. After blood clots, the fluid portion is called serum. HLA typing is performed on the white blood cells known as lymphocytes.
Q: What other testing is performed by the HLA laboratory?
A: The HLA laboratory not only performs HLA typing, we also test for antibodies to HLA. There are 2 specific types of antibody testing that we perform:
- Crossmatch: testing for antibodies specific against a particular donor
- Panel-reactive Antibody (PRA): testing the patient's blood for antibodies against many different HLA antigens
Q: What is a crossmatch?
A: A crossmatch is a laboratory test performed before transplantation to detect antibodies in the recipient’s blood that may destroy the transplanted organ. The test is performed with the white blood cells (lymphocytes) from the potential donor and the serum (the straw yellow-colored fluid formed when blood clots) of the patient.
In cases where lymphocytes from a potential donor are attacked by the patient’s antibodies, transplantation with this donor may not occur and another will be sought.
Q: What is PRA?
A: A PRA test can be performed many different ways. Basically, we take known HLA proteins and react them with a patient’s serum. If the patient has antibodies to a particular HLA protein, the antibodies will bind. We then add other special proteins to allow us to detect that the antibody is bound to the HLA protein. By determining which HLA proteins a patient reacts to, we can determine if a potential patient/donor combination is likely to have a good or bad outcome.
Q: What causes anti-HLA antibodies to develop?
A: Anti-HLA antibodies can be triggered by blood transfusion, multiple pregnancies and by transplantation. Lymphocytes present in transfused blood are the source of the immunization causing anti-HLA antibody development.
Since a person can develop antibodies after a transfusion, it is important for a transplant candidate to submit a blood sample to the HLA laboratory approximately 14 days after each transfusion. The serum will be tested to determine whether anti-HLA antibodies have been produced.
If anti-HLA antibodies were produced as a response to the transfusion, the HLA specificity can be defined and avoided in selection of a suitable organ donor.
Q: Can anti-HLA antibodies change?
A: Yes and no. Once an antibody is made, it doesn’t really change. What changes are the types of antibodies that are made and the amount of these antibodies in the bloodstream. The immune system is very good at changing the antibodies that are made, to make the immune response even better. HLA antibody levels can be high following a transfusion or transplantation but significantly decrease in the months or years following. However, the cells that make antibodies can develop into memory cells and the antibody levels can go from undetectable to extremely high very quickly (within days) if a patient is exposed to a foreign HLA again.
Q: What makes HLA so complex?
A: Finding an HLA-matched donor can be difficult because there are so many different HLA antigens, or proteins. There are 3 different HLA class I antigens: A, B and C. There are several HLA class II antigens but the most commonly tested are: DR and DQ. There are many different antigens within each group; for example there are at least 21 different HLA-A antigens.
HLA antigens are named with the letter of the locus followed by a number designation unique for a particular antigen, i.e. A1 or A24. Each person inherits one A, B, C, DR and DQ antigen from each parent. Thus, we have 2 HLA-A antigens, 2 HLA-B antigens and so on.
In addition, the number of possible combinations of HLA-A with -B and -C and –DR and –DQ makes billions of different HLA types possible.
Q: Why can it be so difficult to find an HLA-matched donor?
A: The best potential for an HLA match is within the family. Each person inherits one A, B, C, DR and DQ antigen from each parent. Thus, we have 2 HLA-A antigens, two HLA-B antigens and so on.
The number of different HLA combinations is limited to the HLA types of the parents. A typical HLA typing would be expressed as: A11, 32; B35, 44; DR1, 7; DQ5, 9. In this case, A11; B35; DR1; DQ5 may be inherited from the mother and A32; B44; DR7; DQ9 from the father.
The combination of HLA-A, B, DR and DQ antigens inherited from each parent is called a haplotype. Each parent has 2 HLA haplotypes one of which will be inherited by each child. For all children sharing the same parents, there will only be 4 possible combinations of HLA antigens or haplotypes. The odds of finding “matches” between siblings greatly increases compared to the general population because we have a 1-in-4 chance of being identical to each sibling.
When an unrelated donor is sought the number of potential HLA combinations becomes so enormous that finding the patient’s exact HLA type may seem like searching for a needle in a haystack.
Q: What is immunogenetics?
A: It is the study of the genetics of the immune system. Among many other things, immunogenetics can include the study of HLA antigens, antibody formation, transplantation rejection and graft-versus-host disease.
Q: If my sibling and I have the same blood group, do we have the same HLA antigens?
A: The A, B and O blood groups and HLA genetic systems are not inherited together. Just as the gene for eye color is separate from the gene that indicates blood group, so are your genes different for HLA compared to blood group genes.
- In kidney transplantation, the donor and recipient must be of the same ABO blood group.
- For bone marrow transplantation, the blood group of the donor is not important. In fact, after bone marrow transplantation, the patient will have the donor’s blood type.