Kidney transplantation offers a life-changing treatment for individuals facing end-stage renal failure. This complex procedure involves placing a donor kidney into a recipient whose own organs are no longer functioning adequately. The primary challenge in this process is the recipient’s immune system, which is programmed to recognize and destroy anything it perceives as foreign. To prevent this destructive response, a compatibility assessment known as Human Leukocyte Antigen (HLA) typing is conducted. This testing determines the degree of biological similarity between the donor and the recipient, directly influencing the likelihood of the body accepting the new organ.
What are HLA Proteins?
Human Leukocyte Antigens (HLA) are proteins that exist on the surface of most cells, acting as a unique genetic fingerprint for that individual. These markers are encoded by genes on chromosome six and are the human version of the major histocompatibility complex. The primary function of HLA proteins is to help the immune system distinguish the body’s own cells (“self”) from foreign invaders like viruses or bacteria. Every person inherits a combination of these markers from their parents.
The HLA system is categorized into two main groups, Class I and Class II, both relevant in transplantation. Class I antigens, specifically HLA-A, HLA-B, and HLA-C, are found on the surface of virtually all nucleated cells. Class II antigens, including HLA-DR, HLA-DQ, and HLA-DP, are restricted to specialized immune cells, such as B-cells and antigen-presenting cells. Identifying these six markers is a foundational step in minimizing the risk of rejection, as the transplanted kidney will express the donor’s unique combination.
The Immune System’s Role in Identifying Foreign Tissue
The immune system mounts a defense whenever it encounters cells bearing non-self HLA markers, interpreting the transplanted kidney as a threat. This defense mechanism is primarily driven by specialized white blood cells known as T-cells, which constantly patrol the body. When these T-cells encounter the donor kidney’s cells, they directly recognize the mismatched HLA proteins as foreign antigens. This recognition triggers an immune response designed to attack and destroy the foreign tissue.
The type of T-cell activated depends on the HLA class encountered; CD8+ T-cells recognize foreign Class I proteins, while CD4+ T-cells respond to Class II proteins. This cellular attack can lead to acute rejection, a swift process where the immune system destroys the graft shortly after surgery. Furthermore, mismatched HLA stimulates B-cells to produce antibodies specifically targeted against the donor’s HLA markers. These anti-HLA antibodies can initiate antibody-mediated rejection, which compromises the transplanted organ’s function.
The HLA Typing and Crossmatching Process
Compatibility assessment involves two main tests: HLA typing and the crossmatch. HLA typing is the initial blood test performed on both the recipient and the potential donor to identify the specific HLA antigens they possess. Laboratories analyze the genes encoding the six primary antigens—HLA-A, HLA-B, and HLA-DR—to determine the number of mismatches between the two individuals. The results are expressed as the total number of differences, where a perfect match is zero mismatches out of six.
The crossmatch is performed just before the transplant, acting as a final safety check. This test involves mixing the recipient’s blood serum (containing antibodies) with a sample of the donor’s white blood cells. If the recipient’s antibodies attack the donor cells, the result is a positive crossmatch. A positive result indicates the recipient possesses pre-formed antibodies against the donor’s HLA, which would lead to immediate rejection. Only a negative crossmatch allows the transplant to proceed safely.
Impact of HLA Matching on Transplant Success
The degree of HLA compatibility between the donor and recipient directly influences the long-term health of the transplanted kidney. A better HLA match, particularly a lower number of mismatches at the HLA-A, HLA-B, and HLA-DR loci, is associated with a lower rate of acute rejection episodes. This improved compatibility also correlates with extended graft survival. Data shows that transplants with zero HLA-B and HLA-DR mismatches demonstrate significantly better one-year survival rates compared to those with three or four mismatches.
A closer match allows physicians to use lower doses of immunosuppressive drugs. These medications are necessary to prevent the immune system from attacking the graft, but they carry risks of infection and other side effects. Minimizing the drug dosage reduces the recipient’s risk of experiencing these adverse effects. Patients exposed to foreign HLA through previous pregnancies, blood transfusions, or prior transplants may develop a high number of anti-HLA antibodies, making them “highly sensitized.” Specialized allocation programs prioritize these highly sensitized patients for compatible kidneys.