HLA Testing

The primary use for HLA testing is to match organ and tissue transplant recipients with compatible donors. 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 Australian bone marrow donor registry. HLA testing is performed and test results kept on file to compare 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 against 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 antibody specificities and the donor HLA typing.

Sometimes HLA gene testing is used to aid in the diagnosis of some autoimmune diseases. 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. Sometimes the body inappropriately produces an immune response against ones own cells, creating antibodies (autoantibodies). Certain alleles of HLA genes have been associated with some of these autoimmune processes. (For more on this, see Common Questions #2).

Transplant recipients - HLA and antibody testing is typically performed when it is first determined that a person needs to have an organ or bone marrow transplant. However, antibody testing may not be done for a bone marrow recipient. HLA results will not change over time.

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 doctor to assess and treat the rejection.

Transplant donors - HLA typing is performed on family members when they have volunteered to see if they are a match for a relative who needs a kidney, liver, lung, bone marrow, or other type of transplant. 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 may be performed just prior to an organ transplant to ensure that there is not 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.

Specific MHC 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 or 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 HLA antibodies to the donor HLA 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 patients are at risk for rejection of the transplant, which may or may not be treatable with various immunosuppressant drugs.

HLA testing is performed in laboratories that specialise in histocompatibility and immunogenetics. 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.

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

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:

No. Although both systems are inherited and are important for tissue compatibility, they are independent of each other.

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 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.