Immunosuppression
Drugs were needed to suppress the body's
immune response to organs and tissues from other humans without suppressing the response to bacteria, fungi, and viruses. A combination of corticosteroid drugs with the antileukemia drug azathioprine (Imuran) was found to do this. With the development of the first immunosuppressive drugs in the mid-1950s, kidney transplants from living donors showed the success of tranplants. Imuran and corticosteroids became the central immunosuppressive regimen in transplant patients in the early 1960s.
In the early 1970s, researchers discovered the
cyclosporine family of immunosuppressants. The drugs block the activity of the lymphocytes called T-helper cells, which initiate the function of the cells that attack foreign tissues. Cyclosporine has potentially harmful side effects such as kidney damage or an increase of hypertension, and it impairs the immune system's ability to fight off infectious organisms. Nevertheless, it has dramatically increased survival rates in a variety of operations since it became available for clinical use in the early 1980s. The success of cyclosporine combined with many surgical refinements opened the door to heart and liver tranplants with success rates similar to kidney transplants.
New drugs continue to be investigated. FK-506 has been found to be more effective than cyclosporine, without side effects, in some clinical trials. Combinations of drugs that act on different pathways of the immune response may be the best approach. Most ideal, however, is specific tolerance to the transplant antigens with no effect on the immune response to other microorganisms.
Tissue Typing
Concurrent with the development of better immunosuppressive drugs and improved surgical techniques, the field of tissue typing, or human leukocyte antigen (HLA) matching, was born. HLA matching is a system of selecting ideal donor-recipient pairs. The aggressiveness of the immune response depends on the genetic gap between the
donor and the recipient. Each person generally has 2 antigens each in the HLA A, B, and DR locus that must be matched. As many as 200 HLA
types were identified through an extensive international effort. The known 200 HLA types are combined in various ways to make up the 6 HLA types that are commonly
matched for transplantation. Ones that are too strong, leading to rejection of grafts, are now being determined. Fortunately, many incompatibilities can be overcome by immunosuppression.
As many as 2,000 recipients have benefited from kidneys shipped to them over long distances, utilizing the
national computerized system that registers the tissue types of recipients. Every time a potential donor is located in the United States, the donor is typed and matched nationally. This type of national sharing is required because the combination of HLA types in any given individual tends to be almost unique. The high degree of variability in HLA types also accounts for why a national bone-marrow donor registry is required to locate someone who would be matched to any given patient.
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