[Note: This entry was actually written in Sep 2009. I changed the posting date to keep my blog entries in chronological order.]

The National Kidney Registry has sent me a swab kit. I need to rub the swab inside my cheek, let it air-dry, put it in a test tube, seal the tube with a stopper, and mail the tube to a test lab.

I assume the purpose of the swab is to get a DNA sample to run a genetic test called the human leukocyte antigen (HLA) typing test.

The immune system contains antibodies that have a wide variety of tips. Each tip will adhere to a different surface molecule called an antigen. When an antibody adheres to an antigen, it reproduces (the new copies will find additional instances of the antigen) and causes the body’s leucocytes (white blood cells) to attack and reproduce (so they will destroy the substance containing the antigen). Normally, the substances that are attacked are microbes that can cause disease.

Human cells are also covered with antigens that would cause an immune response. Through some magical process, the immune system destroys any antibodies that would adhere to the self-antigens before they get into the blood stream. (If the destruction process isn’t complete, then the self-targeting antibodies circulate in the body and eventually adhere to normal cells. This causes leukocytes to attack the cells. This leads to autoimmune diseases like asthma, lupus, or rheumatoid arthritis.)

If chosen at random, the cells in a donor organ (or transfused red blood cells) are unlikely to coated with the same self-antigens as cells in the recipient. When transplanted, the foreign cells will trigger an immune response. If this immune response is not prevented, the recipient will become very sick as the immune system attacks the transplanted cells. The transplanted cells will be killed and the organ will eventually fail. This is called organ rejection.

Part of the effort to reduce the chance of rejection is to choose a donor whose cells are coated with HLAs that the recipient does not carry antibodies for. The most virulent immune response comes from a set of antigens known as blood type. (More on blood type antigens in a later post.) For most transplant recipients, this is the only antigen match required for a successful outcome.

However, just matching blood type antigens isn’t enough sometimes. Some patients who need a transplant start have come in contact with foreign HLAs and start producing antibodies to them. This contact is often due to having received repeated blood  transfusions (often from receiving human-derived EPO during the course of dialysis therapy) or having a previous organ transplant. Women may also develop antibodies for HLAs after becoming pregnant multiple times from the same father. These patients have antibodies that will adhere to the surface of transplanted cells. This will trigger an immune response that leads to organ rejection. In these cases, the recipients will require donors whose cells have surface molecules do not include any of those HLAs.

Matching blood type antigens is fairly easy. There are only two genes involved with a total of eight possible combinations. However, there are many HLA genes, of which three pairs are most influential in organ rejection. Every person receives half of each pair from each parent for a total of six combinations. Each gene may have hundreds of known alleles, meaning there are millions of possible combinations and it is highly unlikely that two unrelated people will match all six by chance. Patients who have become sensitized to non-self HLAs must have a donor who does not have the HLA for which they have antibodies for in order to avoid organ rejection. They will have a much harder time finding a suitable donor. Even if the recipient is not sensitized, getting an organ that is a so-called 6-HLA match can lead to better outcomes.

In all cases, unless the donor and the recipient have identical antigen profiles (probably only occurs when the pair are identical twins), there will be an immune response unless some additional action is taken. Thus, after receiving a transplant, organ recipients will need to suppress their immune system through the use of anti-rejection medication. They will need to take these drugs for the rest of their lives. (More on the the Medicare limit on reimbursement for the cost of these drugs in a later post.) Because the immune system is suppressed, some patients also take anti-infective and anti-ulcer drugs to protect them from opportunistic infections.

For all the risks to the recipient, a kidney transplant is a much better long-term option for most patients than dialysis. (More on dialysis in a later post.)