HLA Matching, Antibodies, and You

Kidney Transplantation: Past, Present, and Future

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The purpose of this booklet is to aid patients' understanding of tissue matching and antibody production. Since matching and antibodies can play an important role in transplantation, we thought we would take the time to explain a few central concepts and ideas important to kidney and/or pancreas transplantation.

What is HLA matching?

When two people share the same HumanLeukocyte Antigens (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 body.

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 important 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 2 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 2 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 2 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 4 chance of being an identical match with your siblings.


		After HLA is determined, there is a second test which will indicate if there is specific immune reactivity between the donor and recipient. This test is the "crossmatch". What is the crossmatch? The crossmatch is a test which determines if the recipient hasantibody 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 particularHLA Not everyone has antibody againstHLA.


		The crossmatch is performed by mixing a very small amount of the patient'sserum with a very small 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 signifies that the patient has the ability 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 HLAantibody production are: transfusions, transplants and/or pregnancies. So, we hope the crossmatch will be negative. A negative crossmatch indicates that the patient does not haveHLAantibodyagainst that particular donor, and a transplant can be performed.


	Since a patient can developantibody after a transfusion, it is very important 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 extremely important 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). What is PRA? PRA (PercentReactive Antibody) is the amount of HLA antibody present in a patient's serum. As stated before, the patient could haveHLAantibody as a result of transfusions, prior transplants, and/or pregnancies. ThePRA 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% (1/2 of 60). The PRA is calculated for each monthly serum sample.


			In addition to determining how much or how littlePRA 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 antibodyspecificities, while others have numerous specificities. We are able to determine the specificity at the same time which we test for the monthlyPRA.

			Therefore, the monthly PRA gives us two very important pieces of information about the patient's serum:

Since HLAantibody can "come and go", it is important to test for thePRA 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 HLAantibody, but it also gives us an array of samples with which we can perform crossmatches for each specific donor. The most recent 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 change? Yes. HLAantibody levels can be high following a transfusion but then decrease significantly months later. 2. Why do I need to submit a monthly sample if I have not received a transfusion? Sometimes, a patient can have antibody that mimics HLAantibody. Even though it is not harmful antibody, it is difficult for us to determine the cause of the antibody production. Sometimes, even a strept throat infection can cause antibody production which can be confused with HLAantibody. So, it is important for us to monitor monthly serum samples and correlate the antibody production with medical events - such as infections, medications, etc. 3. 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 theHLA 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.



4. What are the chances of my cousin or even a friend being a match?

Clearly, the further apart a potential donor is from your immediate 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 respond 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 -GLOSSARY- 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 body. (pg. 2). PRA (Percent Reactive Antibody) - The amount of HLA antibody present in a patient's serum. (pg. 13)




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