HLA testing is generally carried out in the context of organ transplantation, on people preparing to receive or donate an organ. The test can identify inherited HLA (human leucocyte antigen) genes and antigens and detects antibodies against HLA antigens that could cause a transplant to fail; it also makes it possible to identify HLA antigens on blood donors’ platelets, to check transfusion compatibility.
People who are due to have an organ or haematopoietic stem cell transplant are usually tested. Before a transplant, potential donors are tested to assess compatibility with a specific recipient or to be entered on the national transplant register.
Platelet transfusions are sometimes unsuccessful because of HLA antibodies. To improve the response, HLA-compatible donors and recipients are matched in these cases.
A blood sample from a vein
Human leucocyte antigens (HLA) are specialised proteins found on the surface of all the body’s cells except red blood cells. The HLA genes a person inherits are responsible for the expression of specific HLA antigens on the surface of their cells. The test, carried out to check HLA compatibility, identifies the genes coding for HLA and the HLA antigens on the cell surface, and any antibodies against other HLA antigens.
In humans, the HLA genes are located in a region of chromosome 6 called the major histocompatibility complex (MHC). The MHC plays a key role in the immune system, allowing it to distinguish between what belongs to the body itself (“self”) and what is foreign (“non-self”). Any cell recognised as “non-self” can trigger an immune response, including the production of antibodies. HLA antibody testing is therefore carried out on all organ transplant recipients to detect antibodies that could attack the HLA antigens of the donor’s organs or tissues. This test is also carried out for platelet transfusions, to detect any antibodies that could attack the donor’s platelets and cause the transfusion to fail.
In haematopoietic stem cell transplants, the donor’s and recipient’s HLA genes must be the same or very similar, to limit the risk of incompatibility and therefore of graft-versus-host disease (GVHD).
In solid organ transplants, such as kidney, heart or lung transplants, ABO compatibility is essential. After ABO blood group compatibility has been checked, it is also important to check HLA compatibility between donor and recipient. Unlike ABO compatibility, however, a lack of HLA compatibility is less critical as long as the recipient does not develop antibodies against the donor’s HLA antigens. The risk of organ rejection can therefore be limited by giving the recipient immunosuppressant treatment.
Finding compatible donors and recipients can be difficult. This is partly because the HLA gene is polymorphic, i.e. it exists in a great many variants, called alleles. In addition, there are more than 200 genes on chromosome 6 that make up the HLA gene family. Given the very large number of possible combinations and HLA alleles, finding a donor-recipient match can be very complex, especially when the recipient already has anti-HLA antibodies.
However, the HLA genes are located close together and are inherited together as haplotypes: each person inherits one haplotype from each parent. This is why family members are much more likely to be HLA compatible. A recipient’s relatives are often the best donors.