HLA Typing: Purpose, Genetics, Procedure, Interpretation

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HLA typing is a kind of genetic test used to identify certain individual variations in a person’s immune system. The process is critical for identifying which people can safely donate bone marrow, cord blood, or an organ to a person who needs a transplant. HLA stands for human leukocyte antigen, but it is almost always referred to as HLA. HLA typing is also sometimes called HLA matching.

Purpose of HLA Typing

By far, the most common reason for HLA typing is to help determine which people can provide the safest tissue transplants (solid organ or hematopoietic stem cell transplantation). Potential tissue recipients must have the typing, as must anyone who might potentially want to donate tissue. This might include relatives of someone needing a transplant.

People can also volunteer to have their HLA type included in a bone marrow registry, for stem cell transplantation. HLA typing may also be performed on terminally ill or recently deceased people who will be serving as organ donors.

The best possible donors have HLAs that closely match the HLA patterns of the recipient.

This makes it more likely the transplant will successfully treat your disease, and it lowers the risk of complications after transplant, such as organ rejection.

Some people may also need to have a component of HLA typing performed after transplant, to see if their body is making antibodies to the transplanted tissue. This might be one sign that organ rejection is taking place, and the transplant may not be a success. 

Conditions That Require Transplanting

There are many different health conditions that may need to be treated through transplant. For example, various types of blood cancers and genetic blood disorders are treated through stem cell transplantation (taken either from the bone marrow or from the peripheral blood). For example, it is a curative treatment for sickle cell disease.

A solid organ transplant might be necessary for any essential organ that has become severely damaged. This might happen through trauma, infection, autoimmune disease, genetic illness, toxins, or through many other disease processes. For example, one might need a kidney, liver, or lung transplant if one’s own organs very functioning very poorly. Often, a transplant provides the last hope of a treatment cure.

What Is the HLA System?

The HLA system refers to a group of related genes that play an important role in the immune system. Together, the proteins made from these genes form something called the major histocompatibility complex (MHC). These proteins are attached to almost all of the cells of your body (excluding red blood cells).

There are many possible variations in these attached proteins that your other cells can detect. They are part of how your body recognizes which cells belong in your body and which do not.

As an analogy, you can visualize the HLA proteins as different colored strings floating off the cell. In our example, our own cells are programmed to recognize a certain pattern of string colors that belong to us. For example, you could imagine that your HLA types include a black string, a bright blue string, a light violet string, and a yellow string.

If an immune cell notices a cell with an orange HLA protein string, it would send off alarm bells. That warns the cell that it might be seeing something potentially dangerous, like a virus. This might trigger the immune system to attack the cell.

The HLA system plays an important role in immune defense. However, it also helps determine who can give and receive tissue successfully. If the immune system targets the donated tissue as foreign, (i.e., the wrong “color”) it may attack and damage the donated tissue. That’s why it’s important for people to receive donated tissue that has as many matching HLA proteins (i.e., the right “colors”) as possible. 

The Process of HLA Typing

HLA typing assesses the particular HLA genes that you have inherited (i.e., your string colors). Because there are a number of different HLA genes, as well as different variations of these genes, there are very many different possible color combinations that together make up your specific HLA type.

HLA typing also usually includes testing for antibodies targeted to specific HLA proteins. Antibodies are made by part of the immune system. If a person already has an antibody against an HLA protein (i.e., if it already is primed to attack a certain color string), it may attack that protein if it is transplanted. This may cause the transplant to fail. So generally, you shouldn’t receive a transplant from someone if you already have an antibody against one of their HLA proteins.

Similarly, HLA typing also often includes something called lymphocyte crossmatching. Lymphocytes are a type of immune cell. Lymphocyte crossmatching checks to see if the recipient has an antibody against a protein on the donor’s lymphocytes. If so, that person generally shouldn’t receive a transplant from that particular person. These people are at high risk of a transplant that won’t be successful.

Is HLA Typing the Same as Blood Typing?

No. HLA is much more complicated than blood typing because there are many more HLA markers that make a person’s cells unique. There are only eight basic blood types, and many people can safely receive more than one type of blood (depending on their type). To receive only blood from a person, you do not need to be an HLA match because HLA is not present on red blood cells.

However, to receive a solid organ transplant, the recipient must have a compatible blood type with the donor, as well as the best HLA match possible. For stem cell donations, one needs a very strong HLA match, but blood type is not as important as it is for solid organ transplants.

How Are HLA Genes Inherited?

Because the HLA genes are located close together on your DNA, they are usually inherited as a group—you inherit a whole set of colors not just one individual color at a time. Your HLA type is composed of the set of HLA genes you inherited from your mother and the HLA genes you inherited from your father. In our analogy, the HLA genes contain information about the "color of the strings" your cells will have.

Biological parents always share half of their HLA proteins with their child. This is also called a “half match.” Conversely, a child always is a half match with their parents. In our analogy, a child would share half of the colors on his cells with each of his parents.

Siblings who share both parents are most likely to be an identical HLA match. Such siblings have a 1 in 4 chance of being a perfect HLA match (with perfectly matching colored strings).

There is also about a one in two chance that siblings will share half of the HLA markers and be a half-match.

Because siblings only have a one in four chance of being HLA identical, it’s not uncommon for people not to have anyone in their family that is a close match.

For a solid organ transplant (like a kidney) that can be given by living donors, it may be worth getting HLA typing for other members of the family as well: uncles, aunts, (and more) to help find a good match. Because stem cell donations require a higher percentage of HLA matches, it is less likely that a suitable match will be found this way.


Groups of HLA “colors” run in certain ethnic groups. So even if someone in your family isn’t a good match, it may be more likely that someone from a shared genetic heritage will be a match for you. This is part of the reason it may be harder for some people to find a good HLA match than others.

For example, bone marrow registries currently contain fewer potential donors of African American descent. This may make it less likely that these individuals can find a good HLA match from a non-relative.

How Is It Performed?

HLA typing is a genetic test. For the test, you’ll need to give some sort of tissue sample. This is usually from a swab from inside your cheek or from a blood sample drawn from a vein in your arm. Usually, no preparation for the test is necessary. The sample will probably need to be sent to a specialized center for analysis. Since HLA typing is not a commonplace blood test, you may want to check with your insurance carrier ahead of time to assess for coverage and cost.

Interpreting Results

The results from HLA typing are not likely to mean much to you on their own. The HLA proteins have highly technical names. However, your doctor may give you information about your HLA type compared to that of a potential donor. For example, such a test can give information about whether siblings are identically HLA matched or not if the possibility of a stem cell transplant is being investigated. This is the relevant information.

How Many HLA Matches Do You Need?

Ideally, the donor and recipient would be perfectly HLA matched. However, this is not always possible. The details of this depend on the specific type of transplant and on other medical circumstances.

Stem cell transplantation is often a greater challenge than solid organ transplantation in terms of the importance of a good HLA match. In both, there is a risk that the cells of transplant recipient may attack the donated tissue. But in a stem cell transplant, there is also a chance that some of the donated cells may also attack the cells of the transplant recipient. This is known as graft-versus-host disease. So, people receiving stem cell donations usually need to have a higher percentage of matches than people receiving a solid organ.

People receiving solid organ donations tend to do better if they have a better HLA match.

For example, 10 years after a kidney transplant, you are more likely to still have a functioning kidney if you received a kidney with a full HLA match than if you received only a half HLA match.

Different doctors and medical institutions may have different guidelines about the number of HLA matches needed to go ahead with a transplant. But in certain situations, you might still be able to have a transplant with a smaller number of matches.

Your doctor will work with you to find the best treatment option if you haven’t yet found a good transplant match. In some cases, you may want to go ahead with a transplant that isn’t a very good match. In other cases, you may want to receive other treatments while you wait for a better match to potentially become available. It’s challenging to wait, but sometimes that is the best option.

HLA Typing and Tissue Registries

Information about your HLA type is included in databases that link potential donors to recipients. For example, the United Network of Organ Sharing determines who gets organs from deceased donors in the US. It uses information about donors’ and recipients’ HLA types when calculating the best matches for these organs. It is one of many factors that determine who receives them.

Similarly, people are encouraged to volunteer to have HLA typing done, so that information can be added to a registry of potential bone marrow donors. That information is stored in a database. If an HLA match to someone needing bone marrow is found, these people may be contacted to see if they can donate.

A Word From Verywell

HLA typing is a complex topic, and it’s easy to feel lost in the details. Ask your healthcare team as many questions as you need to feel comfortable. The bottom line is that HLA typing is an important step in your healthcare treatment plan. Finding a good match will give you the best chance that your transplant will successfully treat your condition, and that your new tissue will work for years to come. 

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