Transplant Timeline – Immunology

1901-1903: Discovery of ABO Blood Groups: Viennese physician Karl Landsteiner points out that adverse reactions that occur when humans receive blood from animals may also occur when humans receive blood from other humans. His suggestions receive little attention until 1909, when he classifies the human blood into the A, B, AB, and O groups and shows that catastrophic reactions can occur when a person receives blood from a different group. Compatibility is later found to be not only a requirement for transfusion but for transplantation. In 1930, Landsteiner wins the Nobel Prize in Physiology or Medicine "for his discovery of human blood groups."

1944: Research into Rejection: British scientist Peter Medawar discovers that animal embryos exposed to foreign tissues do not reject the tissues and concludes that rejection of a transplant is based on immunologic factors. Meanwhile, Frank Macfarlane Burnet of the University of Melbourne in Australia suggests that the body's immune cells learn very early on to accept whatever tissues are there as part of the body and only attack and reject material that shows up later. Medawar and Burnet go on to be co-winners of the 1960 Nobel Prize in Physiology or Medicine "for discovery of acquired immunological tolerance."

1958: Discovery of First HLA Antigen: French physician Jean Dausset describes the first leucocyte antigen, MAC (now known as HLA-A2). The discovery allows for tissue matching beyond blood types. Dausset is one of three co-winners of the 1980 Nobel Prize in Physiology or Medicine "for their discoveries concerning genetically determined structures on the cell surface that regulate immunological reactions."

1962: Introduction of Imuran (azathioprine): Research by Gertrude B. Elion and colleague George H. Hitchings (two of the three winners of the 1988 Nobel Prize for Physiology or Medicine "for their discoveries of important principles for drug treatment") leads to the development of the anti-rejection drug Imuran, which blocks the body's rejection of foreign tissues.

1983: Cyclosporine Approved for Use: The US FDA approves Cyclosporine, an immunosuppressant drug isolated from a fungus. Cyclosporine revolutionizes organ transplantation because it selectively suppresses the transplant recipient's immune system, allowing the patient to tolerate the grafted organ but preventing routine infections. Cyclosporine was first shown as an immunosuppressive agent by Swiss physician Jean Borel in 1977.

1986: Improving Donor Organ Survival: Researchers Folkert Belzer and James Southard of the University of Wisconsin – Madison develop the UW solution, a synthetic solution that increases storage times from six to 36 hours for organs such as livers and pancreases.

1990: FK506 Available: FK506, or Tacrolimus, under the tradename Prograf, is a derivative of a soil fungus found in Japan. It has immunosuppressive properties very similar to cyclosporine but is 10 to 100 times more potent on a per gram basis.

1995: CellCept Approved for Use: CellCept (mycophenolate) receives FDA approval for the prevention of organ rejection in the case of kidney transplants. It goes on to receive approval for use in heart transplants (February 1998) and liver transplants (July 2000).

1997: Zenapax Approved for Use: The US FDA recommends the approval of Zenapax (daclizumab) for preventing acute organ rejection in patients receiving renal transplants.

1999: New Procedure to Enable Kidney Transplant: Researchers from the University of Maryland Medical Center in Baltimore announce the development of a new procedure called High PRA Rescue (high panel reactive antibody rescue). High PRA can be developed after a pregnancy, a previous blood transfusion, or an earlier kidney transplant. The blood of individuals with High PRA (about 20% of people on the kidney transplant list) has high levels of rejection antibodies, putting sufferers at a greater risk of rejection than cell-mediated rejection. As the antibodies will react with a large portion of the population, the condition significantly increases their waiting time for a kidney.

The High PRA Rescue procedure involves plasmapheresis, in which patients are connected to a machine that removes their blood, separates the serum containing the antibodies, returns the red and white cells and platelets, and replaces the serum with a protein solution. Patients are also treated with three anti-rejection drugs.

1999: Rapamune Approved for Use: The US FDA recommends the approval of Rapamune (Sirolimus) to prevent organ rejection in adult renal transplant patients.