Genes and Organ Transplants

For a person with a seriously impaired organ, a transplant operation may offer the only hope of survival. Successful transplantation requires more than the skills of a surgeon; it also requires a genetic match between the patient and the person donating the organ.

The fate of transplanted tissue depends largely on the type of antigens present on the surface of its cells. Because foreign tissues are usually rejected by the host, the successful transplantation of tissues between different persons is very difficult. Tissue rejection can be partly inhibited by drugs that interfere with cellular immunity. Unfortunately, this treatment can create serious problems for transplant patients, because they may have difficulty fighting off common pathogens and thus may die of infection. The only other option for controlling the immune reaction is to carefully match the donor and the recipient, maximizing the genetic similarities.

The tissue antigens that elicit the strongest immune reaction are the very ones used by the immune system to mark its own cells, those encoded by the major histocom-patibility complex. The MHC spans a region of more than 3 million base pairs on human chromosome 6 and has many alleles, providing different MHC antigens on the cells of different people and allowing the immune system to recognize foreign cells.

The severity of an immune rejection of a transplanted organ depends on the number of mismatched MHC antigens on the cells of the transplanted tissue. The ABO red-blood-cell antigens also are important because they elicit a strong immune reaction. The ideal donor is the patient's own identical twin, who will have exactly the same MHC and ABO antigens. Unfortunately, most patients don't have an identical twin. The next best donor is a sibling with the same major MHC and ABO antigens. If a sibling is not available, donors from the general population are considered. An attempt is made to match as many of the MHC antigens of the donor and recipient as possible, and immunosuppressive drugs are used to control rejection that occurs because of the mismatches. The long-term success of transplants depends on the closeness of the match. Survival rates after kidney transplants (the most successful of the major organ transplants) increase from 63% with zero or one MHC match to 90% with four matches.

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