Kidney Transplantation: Past, Present, and Future
*Note: this is a long document with many pictures. Please be patient while they stream.
The purpose of this booklet is to aid patients’ understanding of tissue matching and antibody production. Since matching and antibodies can play an significant role in transplantation, we thought we would take the time to explain a few central concepts and ideas significant to kidney and/or pancreas transplantation.
What is HLA matching?
When two people share the same H uman L eukocyte A ntigens (abbreviated as HLA ), they are said to be a ",match",, that is, their tissues are immunologically compatible with each other. HLA are proteins that are located on the surface of the white blood cells and other tissues in the figure.
There are three general groups of HLA , they are HLA-A,HLA-B and HLA-DR. There are many different specific HLA proteins within each of these three groups. (For example, there are 59 different HLA-A proteins, 118 different HLA-B and 124 different HLA-DR!) Each of these HLA has a different numerical designation, for example, you may have HLA-A1, while some one else might have HLA-A2.
In the diagram below we can see how a child inherits one HLA in each group, from his/her parents.
If two children inherit the very same HLA from their parents, they are an HLA ",identical match",. While another child in the same family can inherit a different combination of HLA :
It is significant to know that HLA is inherited as a ",set", of the three HLA groups, A, B, DR. This set is known as a ",haplotype",. Below you will notice the father has Two distinct HLA haplotypes.
This child does not match at all with his/her sibling.
You inherit one haplotype from each parent. Therefore, there are a total of four different haplotype combinations from Two parents.
There is a basic rule in HLA inheritance. The rule is: you have a 25% chance of inheriting all of the same HLA (same Two haplotypes) as any one of your siblings, you have a 25% chance of not inheriting any of the same HLA (none of the same haplotypes) and you have a 50% chance of sharing I haplotype with your siblings. Therefore, you have a 1 in Four chance of being an identical match with your siblings.
After HLA is determined, there is a 2nd test which will indicate if there is specific immune reactivity inbetween the donor and recipient. This test is the ",crossmatch",.
What is the crossmatch?
The crossmatch is a test which determines if the recipient has antibody to the potential donor. Antibody is a protein, present in the serum, which could injure the donor’s cells by attacking the HLA . The antibody will only injure the donor’s cells if it is specific for the donor’s particular HLA Not everyone has antibody against HLA .
The crossmatch is performed by mixing a very puny amount of the patient’sserum with a very puny amount of the potential donor’s white cells. If the patient has antibody to the donor’s HLA , the donor’s cells will be injured and this is referred to as a ",positive crossmatch",. A positive crossmatch is a strong indication against transplant, since it represents that the patient has the capability to attack the donor’s cells, and would, most likely attack the donor’s implanted kidney.
Notice how the patient’s antibody fits the donor’s HLA just as a lock and key. This means that somehow, the patient has developed an antibody to the donor’s HLA type.
There could be any number of reasons why the patient could have antibody to the donor’s HLA . The most common causes of HLA antibody production are: transfusions, transplants and/or pregnancies. So, we hope the crossmatch will be negative. A negative crossmatch indicates that the patient does not have HLA antibody against that particular donor, and a transplant can be performed.
Since a patient can develop antibody after a transfusion, it is very significant to submit a blood sample to the Tissue Typing Laboratory no later than 7-14 days after each transfusion.
At any time, a patients may request a kit (tube and packaging material) from the lab, for a posttransfusion sample. It is utterly significant to inform us each time that you receive a transfusion. This will help us to keep track of your
post-transfusion antibody levels (your PRA ).
PRA ( P ercent R eactive A ntibody) is the amount of HLA antibody present in a patient’s serum. As stated before, the patient could have HLA antibody as a result of transfusions, prior transplants, and/or pregnancies. The PRA is determined by testing the patient’s serum to a panel of 60 different types of HLA . If, for example, the patient’s serum reacts with 30 out of 60 HLA , then the patient’s PRA is 50% (1/Two of 60). The PRA is calculated for each monthly serum sample.
In addition to determining how much or how little PRA a patient has, we need to know how specific the antibody is. That is, is the antibody specific to a particular HLA . For example, if you received a transfusion from a donor with HLA-A2, you may develop antibody to A2. That’s antibody specificity. Some patients have one or two antibody specificities, while others have numerous specificities. We are able to determine the specificity at the same time which we test for the monthly PRA .
Therefore, the monthly PRA gives us two very significant chunks of information about the patient’s serum:
Since HLA antibody can ",come and go",, it is significant to test for the PRA regularly. For this reason, we mail a tube to the patient, for a blood sample, on a monthly basis. Monthly testing not only gives us a continuous ",look-see", at the patient’s HLA antibody , but it also gives us an array of samples with which we can perform crossmatches for each specific donor. The most latest monthly sample is used as the current sample, and must always be included in the pretransplant crossmatch.
Most frequently asked questions
1. Can my antibody switch?
Yes. HLA antibody levels can be high following a transfusion but then decrease significantly months later.
Two. Why do I need to submit a monthly sample if I have not received a transfusion?
Sometimes, a patient can have antibody that mimics HLA antibody . Even tho’ it is not harmful antibody , it is difficult for us to determine the cause of the antibody production. Sometimes, even a strept mouth infection can cause antibody production which can be confused with HLA antibody . So, it is significant for us to monitor monthly serum samples and correlate the antibody production with medical events – such as infections, medications, etc.
Three. If my sibling and I have the same blood group, then why wouldn’t we have the same HLA ?
The ABO blood group genetic system and the HLA genetic system are not inherited together. So, just as your gene (the DNA ) for eye color is separate from your gene (the DNA ) for your blood group, so is your DNA for HLA . All of these genes are inherited independently from each other.
Four. What are the chances of my cousin or even a friend being a match?
Clearly, the further apart a potential donor is from your instantaneous family, the less likely they are to be an identical match. In the case of cousins, your chance of being identical is ",1 in 16",. In the case of a friend, then your chances vary depending on how common your HLA is.
We hope this booklet was helpful in your understanding of HLA matching and antibodies. Your tissue typing laboratory staff is always willing and enthusiastic to react to your questions and concerns.
If you have any questions or would like a further explanation of any of the test procedures? please do not hesitate to call us at (313) 647-2774.
Cynthia A. Schall, (CHS)ABHI James R. Baker, Jr., M.D. Supervisor Director
antibody – A protein, present in the serum, which could injure the donor’s cells by attacking the HLA. (pg. 9)
Antibody Specificity – Antibody specific to a particular HLA. (pg. 14)
Crossmatch – A test which determines if the recipient has antibody to the potential donor. (pg. 9)
Haplotpe – A set of HLA which are inherited from a parent. (pg. 6)
HLA (Human Leukocyte Antigens) – Proteins located on the surface of the white blood cells and other tissues in the bod. (pg. Two).
PRA (Percent Reactive Antibody) – The amount of HLA antibody present in a patient’s serum. (pg. 13)