Rejection and recipient age.
In transplantation the risk of acute rejection decreases with recipient age. This is clearly illustrated in transplantation of a non-vascularised tissue, such as the cornea. In vascularised transplants, such as kidneys, acute rejection decreases with recipient age, but the phenomenon is obscured by the fact that chronic allograft nephropathy increases with age, and is further confounded by increased death from infectious disease and drug-related causes. The underlying cellular mechanisms responsible for this weakening of rejection are discussed, as is defective signal transduction leading to decreased activation of cells and decreased resistance to immunosuppressive drugs. This supports a view that less intensive immunosuppressive drug therapy is desirable in elderly recipients. Although pharmacokinetic studies are documented, there are no routine assays to measure efficacy of these drugs in individual patients. In summary, the decline in acute rejection with increasing recipient age may be due both to immunosenescence and decreased resistance to immunosuppressive drugs. Future assays to test these mechanisms could be used to tailor therapy to individual needs.
Bradley
Benjamin A
BA
University of Bristol Department of Transplantation Sciences, Paul O'Gorman Lifeline Centre, Southmead Hospital, UK. ben.bradley@bris.ac.uk
D000208:Acute Disease; D000375:Aging / Q000276:immunology*; D000818:Animals; D002102:Cadaver; D016039:Corneal Transplantation; D016207:Cytokines / Q000378:metabolism; D004351:Drug Resistance; D006084:Graft Rejection / Q000503:physiopathology*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000254:growth & development; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D008658:Inactivation, Metabolic; D016030:Kidney Transplantation; D019520:Living Donors; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013950:Thymus Gland / Q000254:growth & development / Q000276:immunology
D016207:Cytokines; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin