Table of Contents
Kidney transplantation involves the introduction of foreign antigens that are recognized by the patient’s immune system. For this reason immunosuppression is required to prevent rejection. Cross matching is required to determine if a transplant is compatible. HLA testing informs the long term prognosis of the allograft.
Matching
People may think the donor kidney has to be a genetic match to the recipient. This is not the case. What is required for a kidney to be an acceptable “match” is that the donor not have pre-formed antibodies against the kidney. If the recipient has pre-formed antibodies against the donor kidney there will be hyperacute rejection with the graft thrombosing within minutes of anastomosis.
Two things are required for a kidney to be an acceptable match.
- ABO blood type compatibility. This is in general, not universal. There are exceptions
- There is a subtype of blood type A, A2 that is less immunogenic. It may be transplanted if the recipient does not have preformed antibodies.
- Negative crossmatch testing. This is done by either:
- Complement mediated cytotoxicity. Donor lymphocytes incubated with patient’s serum
- Flow cytometry
There also are desensitization protocols for both ABO and a positive cross match. However, these are not mainstream.
How does someone get pre-formed antibodies against a kidney donor? The most common ways are exposure to the foreign antigens through:
- Pregnancy
- Blood transfusion
- Prior transplant
In the absence of ABO incompatibility or pre-formed antibodies immunosuppression is sufficient to prevent rejection. But there’s more…
Major Histocompatibility Complex (MHC) and Human Leukocyte Antigens (HLA)
The Major Histocompatibility Complex (MHC) is a region of genes on chromosome 6 that code for proteins that are present on cells. These proteins are called Human Leukocyte Antigens (HLA).
- There are major 6 HLA antigens in the immune system
- You have 2 of each, 1 from each parent.
- Class I (HLA A,B,C)
- On all nucleated cells
- Class II (HLA DP, DQ, DR)
- On antigen presenting cells
- Can be expressed on epithelial and vascular endothelial cells if exposed to proinflammatory cytokines such as Interleukin- 2 (IL-2)
None of these have to “match” for a kidney transplant to be successful with immunosuppression. However, the higher the degree of matching, the better the long term prognosis of the kidney.
Three of these antigens are most relevant for the immunologic risk of kidney transplantation as they have the highest degree of polymorphisms:
- HLA A
- HLA B
- HLA DR
As one has 2 of each of these HLA antigens there are 6 tested for. The better matched these HLA antigens are, the better the prognosis of the kidney allograft. A 6 antigen matched kidney has the best prognosis and these are given priority in the kidney allocation system.
Matching vs Mismatching
Assessment of this genetic compatibility often refers to the number of mismatched HLA antigens as opposed to the number of matched HLA antigens. This is because the donor may be homozygous for one (or more) of these antigens. As an example HLA A2 is prevalent enough that homozygosity is common.
If the donor has HLA A2/A2 and the recipient has HLA A1/A2 – this would be classified as a 0 antigen mismatch as opposed to 1 antigen match for HLA A.
Summary
Human leukocyte antigens (HLA) are the antigens that provide the immunologic risk of rejection. The presence of preformed antibodies are assessed by crossmatching and make a kidney incompatible for transplant even with immunosuppression. If crossmatching is negative, kidney transplant can occur even if the HLA antigens in the donor differ from that of the recipient. A lower number of HLA mismatching however, portends a better long term prognosis for the transplant. In almost all transplants indefinite immunosuppression is required.
