Histocompatibility Testing: Bridging the Gap for Successful Transplantation

Introduction

Histocompatibility testing is also called tissue typing. This procedure helps in finding the best possible organ for transplantation. During this test, the blood sample of the patient is collected and sent to histocompatibility and immunogenetics laboratories to have this test. This test helps in successful solid organ transplantations and hematopoietic stem cell transplantation by performing HLA (human leukocyte antigen) genotyping in donors as well as recipients to estimate the resemblance of the match and to also detect any mismatches during transplantation.

What Is Being Tested in Histocompatibility Test?

• A histocompatibility blood test is done to examine the proteins or antigens called human leukocyte antigens (HLAs). These proteins are usually found on the surface of almost every cell in the human body except red blood cells. These are present abundantly on the surface of white blood cells. These proteins help the immune system to find the difference between body tissue and substances that are not from the body. The HLA genes that a person inherits from their parents are responsible for the presence of HLA antigens on the cell's surface.

• Therefore histocompatibility test helps in identifying the major HLA antigens that are present on the surface of patient cells and the presence of antibodies to HLA antigens, and the genes that are responsible for HLA antigens to match the donors and recipients.

What Is the Importance of HLA?

In human bodies, the HLA genes are usually present on chromosome 6, which is called the major histocompatibility complex (MHC). This complex plays an important role in the management of the immune system. This helps in the functioning of the body’s immune system by distinguishing between the self or on-self (foreign) substances. These foreign or non-self substances can trigger the immune system leading to the production of antibodies to fight these antigens. Therefore the HLA antibody test or histocompatibility test is performed on the recipients to determine if they have respective antibodies that would target or attack the donor’s organs.

In the case of a hematopoietic stem cell (HSC) transplant, the HLA genes of the recipient as well as the donor must be the same for the transplantation to prevent any complications such as graft-versus-host disease (GVHD - a systemic disorder in which graft's immune cells identify the host cells as foreign and attack the recipient's body cells).

In the case of solid organ transplants such as heart, kidney, or lung, matching the blood group is essential. Therefore after matching the blood types of the recipient and donor, HLA antigens are also matched, but it is not as critical as matching the ABO blood groups. Moreover, various drugs can be prescribed to suppress the immune system of the recipient to minimize organ rejection.

What Are HLA Antibodies?

HLA antibodies are produced by the body’s immune system, and these can cause some serious damage to the kidney if they find any difference in the human leukocyte antigens. A person may have HLA antibodies if they have -

• A history of transplants that failed.

• History of blood transfusions.

• Been pregnant.

HLA antibodies may reappear or disappear over time, so that is necessary to test for these antibodies regularly. In case a patient is going for a transplant, they must be tested for HLA antibodies at least once every three months.

How Is the Test Used?

The primary use of histocompatibility test is used to match organ and tissue transplant recipients with compatible donors. Along with that, it also includes checking for the presence of antibodies in the recipient's body that may target the donated organ or tissue as an immune response.

There are usually three components of histocompatibility testing which include -

• HLA Antigen Typing of Donors and Recipients - This involves testing the HLA alleles, in which any family member volunteering to donate hematopoietic stem cells or an organ is being tested for HLA antigen to check their compatibility with the relative (recipient) who needs a transplant.

• HLA Antibody Screening of Recipients - In this step, the recipient is checked for the presence of any antibodies that would target the donated organ. This test must be periodically performed to check if the recipient has developed any HLA antibodies. This can be done before the transplant or post-transplant to prevent graft failure.

• Lymphocyte Crossmatching (Donor-specific) - This step is usually done in a few cases after the identification of potential donors. This helps in determining if the recipient has antibodies against the antigens present in the donor’s lymphocytes (a type of white blood cell). The blood sample is taken from the recipient and is mixed with the sample of donors containing white blood cells (T and B lymphocytes). Any reaction detected would indicate incompatibility between the recipient and donor.

What Does the Test Result Mean?

During the HLA test, specific genes or antigens are examined to ensure solid organs or hematopoietic stem cell transplant compatibility. The test is done by taking a blood sample from the vein in the arm. However, the sample can also be taken by taking a swab from the inside of the cheek (buccal swab).

The results of the histocompatibility test of the recipient are compared to the donor’s result. This shows how many of the antigens match and how many mismatches. The result with zero mismatches indicates a high possibility that the organ or tissue will not be refused by the recipient.

Moreover, the absence of recipient HLA antibodies to that of donor HLA antigens is very important. As the presence of HLA antibodies means the immune system of the recipient body is targeting the donor’s organ, which will increase the risk of organ rejection.

What Are the Risk Factors of the Histocompatibility Test?

Usually, there are no risks involved in this test, and it is a simple test and does not cause any complications. However, there are still some minor risk factors involved while drawing the blood, which include -

• Fainting or feeling lightheaded.

• Hematoma (building up of blood under the skin).

• Excessive bleeding.

• Multiple punctures to locate veins.

• Infection.

Conclusion

Histocompatibility testing is done prior to any planned transplantation of organs or hematopoietic stem cells. This is a safe and short-duration test without any complications, and results can be available within a day or two. It plays a key role in providing information on whether the recipient body will accept the donor organ or stem cells and can help in preventing any complications.