CHAPTER 8 Interleukin-2 receptor antibodies for cardiac allograft

• Allograft rejection Rejection involves cell- and antibody-mediated organ injury occurring as the result of recognition of an allograft as nonself. This process is categorized histologically and immunologically into three major types: hyperacute, acute and chronic. Hyperacute rejection is mediated by pre-existing antibodies to allogeneic antigens on the vascular endotheli­ al cells within the donor organ. Donor recipient human leukocyte anti­ gen (HLA) and ABO blood-group cross-matching are used to prevent hyperacute rejection [2]. Acute rejection is primarily a cell-mediated process that most commonly occurs from the first week to several years after transplantation. After heart transplantation [24], 61% of patients remain rejection free after the first posttransplantation month, 38% of patients are without rejection by 6 months, and 34% of patients are without rejection by 2 months. The hazard function for initial rejection peaks at approximately 1 month. Chronic rejection, or late graft failure, is an irreversible gradual deterioration of graft function that OCCurS in many allografts months to years after transplantation as the result of intimal thickening and fibrosis [2]. Cardiac allograft vasculopathy is an­ giographically evident in ~45% of heart trans plant recipients who sur­ vive ~3 years [39]. This form of rejection involves a variety of immune­ system components: T cells, cytokines, macrophages, and adhesion mol­ ecules [3]. Preventing or reducing the rate of acute rejection episodes does not only avoid or decrease acute allograft damage, but is expected to have a substantial impact on the rate of chronic rejection because repeated or severe episodes of allograft rejection has been correlated to the devel­ opment of cardiac-allograft vasculopathy, the main cause of death after the first year in transplant recipients [11, 17, 39,42].