Patient Test Information

HLA Testing

Also known as:

Tissue Typing; HLA Typing; Histocompatibility Testing; HLA Crossmatching; HLA Antibody Testing/Screening/Identification

Formal name:

Human Leukocyte Antigen; HLA Oligotyping; HLA Sequence-based Typing

Related tests:

Blood Typing; HLA-B27; HLA-A, B, C, DR and DQ

Why Get Tested?

To identify which human leukocyte antigen (HLA) genes and antigens a person has inherited, primarily to match up donors and recipients of organ and bone marrow transplants and to detect antibodies to HLA antigens that would cause transplants to be unsuccessful

When to Get Tested?

Most often, transplant recipients are tested when it is determined that they need an organ or bone marrow transplant, prior to seeking and selecting a suitable donor; potential donors are tested when they are being evaluated for compatibility with a specific recipient or are signing up with a national donor registry.

Sample Required?

A blood sample drawn from a vein in your arm; sometimes, for HLA typing, a swab from the inside of the cheek (buccal swab)

Test Preparation Needed?

None

How is it used?

The primary use for human leukocyte antigen (HLA) testing is to match organ and tissue transplant recipients with compatible donors. It identifies the major HLA genes a person has inherited and the corresponding antigens (proteins) that are present on the surface of their cells. These antigens help the body's immune system distinguish which cells are "self" and which are "foreign" or "non-self." Any cells that are recognized as "non-self" can trigger an immune response, including the production of antibodies.

HLA testing also includes screening transplant recipients for the presence of antibodies that might target the donated tissue or organ as part of an immune response.

HLA testing is important in medicine when transplanting tissue or an organ(s). In bone marrow transplants, for instance, the HLA genes and antigens that the donor and recipient have need to be the same or match as closely as possible for a transplant to be successful and for the tissue to not be attacked or rejected by the recipient's immune system.

Different kinds of transplants necessitate different levels of matching between donor and intended recipient. This may determine which HLA tests are performed and which HLA genes are tested for.

There are typically three components of HLA testing used to determine compatibility:

  • HLA typing of donors and recipients - this step involves identifying HLA alleles. It may involve serological HLA testing or molecular (DNA) typing.

    Family members who volunteer to donate bone marrow or an organ are HLA tested to see if they are a match for the relative who needs a transplant.

    If people want to make themselves available to donate bone marrow to anyone who needs it, they can sign up with a national registry such as the United States National Marrow Donor Program. HLA testing is performed and test results are kept on file to compare with results from those people who are seeking a match.

  • HLA antibody screening of recipients - HLA antibody testing is performed on the recipient to determine if there are any antibodies present that would target the donated organ or tissue. Some people have HLA-specific antibodies that have developed following an exposure to non-self antigens. There are essentially three reasons for exposure to non-self HLA: pregnancy, particularly multiple pregnancies (from exposure to the father's HLA that have been passed on to the fetus), blood or platelet transfusions, or previous organ transplant(s). Once present, HLA antibodies must be considered during matching because they will potentially attack donor tissues that have the corresponding HLA type.

    HLA antibody testing may be periodically performed and updated to determine if the person waiting for a matching organ to become available has developed additional HLA antibodies. HLA antibody assessment can also be used post-transplant to determine if the recipient has developed new or increased levels of antibodies to the donor.

  • Lymphocyte crossmatching (Donor-specific) - This step occurs after a potential donor has been identified. It helps determine if the intended recipient has antibodies directed against antigens present on the donor's lymphocytes. Serum from the intended recipient is mixed with white blood cells (T and B lymphocytes) from the donor. Any reaction detected (a positive result) would indicate likely incompatibility between the two. The crossmatch result should always be interpreted along with known information regarding the recipient's HLA antibodies and the donor's HLA typing.

Sometimes HLA gene testing is used to aid in the diagnosis of an autoimmune disease. The HLA system is one of the mechanisms involved in the body's recognition of "self" and "non-self" antigens and the immune response to foreign substances. The body can inappropriately produce an immune response against its own cells, producing antibodies (autoantibodies). Certain disease states have been found to be associated with particular HLA antigens, such as ankylosing spondylitis which is associated with HLA-B27. HLA typing may also be important in preventing reactions to certain medications as side effects have been noted with certain drugs and specific HLA types. (For more on this, see Common Questions #2).

When is it ordered?

Transplant recipients: HLA gene or antigen and antibody testing is typically performed when it is first determined that a person needs to have an organ or bone marrow transplant. HLA gene and antigen results will not change over time, but HLA antibody testing may be done periodically and after events, such as a pregnancy or a blood transfusion, to see if the potential recipient has developed additional HLA antibodies. Sometimes HLA antibodies develop in those who receive frequent blood or platelet transfusions. Identification and periodic monitoring of the antibodies may be necessary.

HLA antibody assessment is also used post-transplant to determine if the recipient has developed new or increased levels of antibodies to the donor's transplanted organ. The presence of antibodies to donor antigens, along with other assessments such as a tissue biopsy sample of the transplanted organ, may indicate that the recipient is experiencing rejection of the transplanted organ. This information is important for the health practitioner to assess and treat the rejection.

Transplant donors: HLA gene or antigen typing is performed for family members when they have volunteered to see if they are a match for a relative who needs a kidney, liver, bone marrow, or other type of transplant. Living unrelated persons may also be tested as potential donors for organ transplant, and this is frequently the case for kidney transplants. HLA typing is also performed on unrelated individuals who wish to become a bone marrow donor through the donation registry.

When an organ is from a deceased donor, HLA testing is performed to match it as quickly as possible to a potential recipient or recipients. The amount of time available to ensure the greatest viability of the organs or tissues ranges from a few hours to no more than a day or two.

Crossmatch testing is done after a potential donor has been identified through HLA typing. This test is typically performed just prior to an organ transplant to ensure that there is no mismatch. In the case of living donor transplantation, the crossmatch compatibility is usually performed more than once, when the donor is initially identified and again just before the actual transplant procedure.

What does the test result mean?

Specific HLA genes or antigens are identified during HLA typing for organ and tissue transplant compatibility. The genes and/or antigens of transplant recipients are compared to those of potential donors. Results indicate how many antigens match and how many mismatches are present. The greater the number of matches the more likely the transplant will succeed. "0 mismatches" indicates a high probability that the organ or tissue will not be rejected by the recipient.

The absence of recpient HLA antibodies to the donor HLA antigens is very important. Matching a donor with a recipient who has developed antibodies must be carefully considered because the more HLA antibodies a person has developed, the higher the probability for rejection.

A positive (reactive) crossmatch result is usually interpreted as a high risk transplant. These people are at risk for rejection of the transplant, which may or may not be treatable with various immunosuppressant drugs.

Is there anything else I should know?

HLA testing is performed in laboratories that specialize in histocompatibility and immunogenetics and that are often accredited by the American Society of Histocompatibility & Immunogenetics (ASHI) or the College of American Pathology (CAP). Histocompatibility involves testing donors and recipients to see if they are HLA matches. Immunogenetics is the study of the relationships between the immune system, genetics, and disease development.

What is being tested?

Human leukocyte antigens (HLA) are part of the major histocompatibility complex or MHC. They refer to certain specialized proteins (antigens) present on the surface of all nucleated cells in the body and the genes that code for them. Everyone has an inherited combination of HLA antigens present on the surface of his or her white blood cells (leukocytes) and other cells that contain a nucleus. HLA testing identifies the major HLA genes a person has inherited and their corresponding antigens that are present on the surface of their cells.

HLA antigens and the MHC system play an important role in the management of the immune system. They help the body's immune system distinguish which cells are "self" and which are "foreign" or "non-self." Any cells that are recognized as "non-self" can trigger an immune response, including the production of antibodies. HLA antibody testing is also performed on transplant recipients to determine if there are any antibodies present that would target the donated organ or tissue.

This is important in medicine when transplanting tissue or an organ(s). In bone marrow transplants, the HLA genes that the donor and recipient have need to be the same or match as closely as possible for a transplant to be successful and for the tissue not be attacked or rejected by the recipient's immune system. Also, bone marrow donors and recipients must match closely so that the immune cells (lymphocytes) in the donated bone marrow do not attack the recipient's cells in a process called graft-versus-host disease (GVHD; see Common Questions #4).

In solid organ transplants, such as kidney or lung transplants, it is ideal to match the antigens between the donor and recipient; however, the typing incompatibilities are less critical as long as the recipient has not produced antibodies directed against donor's antigens. Various drugs may be administered to help suppress the recipient's immune system in order to minimize organ rejection.

When the donor organ is compatible with the intended recipient, it is less likely to be rejected in the immediate post-transplant period. HLA testing, along with ABO blood typing, is used to identify and match organ and tissue transplant donors with recipients who have the same or an acceptable number of matching HLA genes and antigens.

Finding a donor who is compatible with an intended recipient may sometimes be difficult. Part of the reason is because each particular HLA gene can have numerous possible forms or variations (alleles). This is referred to as polymorphic. In addition, there are more than 200 genes that make up the large "gene family" of the HLA system. With many different possible combinations and numerous HLA genes to take into account, it can be a challenge to find a suitable donor.

However, HLA genes that are located close together, as seen on chromosome 6, are inherited together as groups known as haplotypes; thus, a child inherits one haplotype from each parent. Because of this, there is a greater chance that family members will have the same group of HLA genes compared with non-related potential donors. Often, a recipient's parents, children, or siblings may serve as the best transplant matches.

Example of inheritance of HLA haplotypes

Read the article on The Universe of Genetic Testing for more on inheritance and the HLA system.

How is the sample collected for testing?

A blood sample is obtained by inserting a needle into a vein in the arm. Sometimes, for HLA typing, a swab of cells is collected from the inside of the cheek (a buccal swab).

NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.

Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.

Is any test preparation needed to ensure the quality of the sample?

No test preparation is needed.

  1. Other than organ and tissue compatibility testing, what else is HLA gene and antigen testing used for?

    Historically, HLA testing was used to help identify someone (forensic testing) or to determine if people were related (parentage testing), although now there are other, more specific molecular tests available for these purposes.

  2. Are there reasons to test for a specific HLA gene allele?

    Yes. Some HLA gene alleles are associated with certain diseases and autoimmune disorders. They are not diagnostic of the disorders but can be useful in helping to confirm or exclude a diagnosis. Relationships have also been documented between certain alleles and sensitivities to specific drugs. Associations include:

    Gene/Antigen Disorders and Associations
    HLA-B27 Ankylosing spondylitis, Juvenile rheumatoid arthritis, Reiter's syndrome
    HLA-DQ2 and HLA-DQ8 Celiac disease
    HLA-DR15 and HLA-DQ6 Narcolepsy
    HLA-B*5701 Abacavir hypersensitivity
    HLA-B*1502 Carbamazepine hypersensitivity

     

  3. Is my blood type (ABO) related to my HLA genes and antigens?

    No. Although both systems are inherited and are important for tissue compatibility, they are independent of each other. The ABO system is located on chromosome 9 and the HLA system is on chromosome 6.

  4. What is graft versus host disease (GVHD)?

    GVHD is a condition that occurs when the immune cells from transplanted donor bone marrow begin to attack the recipient's cells and tissues. The recipient's immune system does not initiate this response.

    Bone marrow is the soft tissue in the center of bones that, in part, produces red blood cells (RBC) and white blood cells (WBC). In GVHD, one type of donor WBCs, T-lymphocytes, produce an immune response against "foreign" recipient cells and tissue. This condition can be mild or severe and sometimes can be life-threatening. It can be acute, occurring within 100 days after the transplant procedure, or can be chronic, typically developing over a longer period of time.

    The greater the number of HLA allele matches between bone marrow donors and recipients, the less risk of developing GVHD. Sometimes the condition may be treated with immunosuppressive medications that decrease the immune response by the donor bone marrow.