Everyone knows that successful organ donation requires good matches, but what do we mean by HLA typing?
Human leukocyte antigens– or markers– are found in most cells of each person’s body. These markers define the proteins that are “you”, versus proteins that are foreign and potentially viruses, pathogens, or abnormal cells. Think of these markers as security guards that allow the immune system to determine which cells do or do not belong in your body. The security guards also have good memories: if they have seen a “non-you” protein before (e.g., during multiple pregnancies, blood transfusions, or prior transplants), they can act quickly, and already have antibodies in wait to quickly attack.
If a donor and a potential recipient have poor compatibility in HLA markers, there is a strong chance the body will reject a donated organ.If a potential recipient already has antibodies ready to respond to a “non-you” protein, an immediate “antibody-mediated” rejection occurs.
The closest matches between donors and patients are usually siblings and family members, as HLA is genetically determined. However, there are other ways to minimize rejection by determining HLA histocompatibility in the matching and offer process. Tests include:
- ABO blood group compatibility as a mismatch in blood groups usually results in a quick rejection
- Tissue typing that uses just the donor’s physical blood sample
- Physical cross-matching that uses samples from both the recipient and donor that are then mixed together to see if the recipient’s antibodies attack (which is called a positive cross match). This type of testing is labour intensive and can be logistically challenging.
- Panel reactive antibody testing which tests the blood of patients awaiting transplant for reactive antibodies against a random panel of cells, indicating an above-average reactive system. These patients may be designated as “highly sensitized”. About 10% of waitlisted patients in the US are highly sensitized.
- Virtual crossmatch uses a physical test of the recipient’s anti-HLA antibody typing and the donor’s HLA typing, performed independently, to predict the result of a physical cross match or the post-transplant outcome. This typing can be done at varying levels of granularity, referred to as field level resolutions. Field 1 resolution may indicate a donor has a B44 HLA phenotype. If a patient has an antibody at the field 2 resolution of B44:02 but not B44:03, predicting whether or not there is a positive cross match is not possible without knowing the field level of the donor. Some labs report donor genotyping at a lower resolution.
Virtual cross-matching is less complex and labour intensive than physical crossmatching. It can be used at the time or organ allocation to predict compatibility, and after allocation to potentially eliminate the need for a physical cross-match, which can increase the cold ischemia time (increase is associated with delayed graft functions, dicards, and graft failure). The benefits are clear, yet virtual cross-match is not used routinely in the United States. Afflo allows both donor labs and recipient labs to report at a higher field level than any other commercial system. This will no doubt lead to better matches, and better outcomes, especially for hard-to-match, highly sensitized patients.