Transplant Rejection

For medical transplantation to be successful, physicians must elude the combative efforts of the body’s complex immune system, which fights to protect the body from infections of all sorts.

Central to the functioning of the immune system is its ability to distinguish between invading or foreign matter, which should be attacked, and matter that is a normal part of the body, which should not be attacked.

This recognition system uses specific markers called histocompatibility antigens that are on the surface of all cells in an individual’s body. The immune system attacks anything that lacks these histocompatibility antigens or has antigens different from those found in the rest of the body, such as those found on invading viruses, bacteria, or other microorganisms.

This recognition system causes the immune system to attack transplanted tissues that have different antigens because it has no way to distinguish between harmful and beneficial foreign matter.

There are over 200 different histocompatibility antigens, with each individual having a specific set of them. The odds that two unrelated people will have the same set of histocompatibility antigens are about one in 30,000.

Transplant surgeons attempt to match histocompatibility antigens of the donor and the recipient as closely as possible in order to minimize rejection. In most cases, the match will not be exact, and the recipients must take drugs to suppress the immune response.

The first drugs that were used were azathioprine and prednisone. But these drugs suppress the entire immune system, leaving the recipient vulnerable to infections and certain cancers. They also have toxic side effects.

A major breakthrough in immune suppression was the development of cyclosporine, a natural product derived from a fungus found in soil. Cyclosporine suppresses the part of the immune system involved in organ rejection with less severe impact on other parts of the immune system.

A few years later, the drug tacrolimus (FK-506) was found to be even more effective for kidney, liver, heart, and lung transplants. However, patients who take these two drugs still face some increased risk of infection and cancer, and the drugs can cause kidney damage. Doctors often use a combination of immune-suppressing drugs to limit these side effects.