Antibody-mediated rejection (AMR) is a major cause of late kidney transplant failure. It is important to have an understanding of human-leukocyte antigen (HLA) typing including well-designed studies to determine anti-MHC-class-I-related chain A (MICA) and antibody rejection pathogenesis. This can allow for more specific diagnosis and treatment which may improve long-term graft function. HLA-specific antibody detection prior to transplantation allows one to help determine the risk for AMR while detection of DSA along with a biopsy confirms it. It is now appreciated that biopsy for AMR does not have to include diffuse C4d, but does require a closer look at peritubular capillary microvasculature. Although plasmapheresis (PP) is effective in removing alloantibodies (DSAs) from the circulation, rebound synthesis of alloantibodies can occur. Splenectomy is used in desensitization protocols for ABO incompatible transplants as well as being found to treat AMR refractory to conventional treatment. Also used are agents targeted for plasma cells, B cells, and the complement cascade which are bortezomib rituximab and eculizumab, respectively. 1. Understanding HLA There are 20 class I genes and in transplantation HLA-A, B, and C are the classic genes referenced to when typing the recipient [1]. Class I major histocompatibility complex (MHC) molecule processing and loading of peptides occurs in all nucleated cells, where class II MHC molecule involves primarily B cells, macrophages, and dendritic cells by method of endocytosis and phagocytosis. Class II MHC molecule nomenclature is designated by class (D), family (M, O, P, Q, R), and chain (A or B). Late antibody-mediated rejection (AMR) is a major cause of late kidney transplant failure and several developments in understanding of pathogenesis allow for improvement of diagnosis, treatment, and prevention. This review will concentrate on reviewing the pathogenesis, diagnosis, and treatment of AMR. 2. Pathogenesis of HLA Antibodies Not only can antibodies form against HLA molecules, but to endothelial-cell antigens and across ABO blood group [2]. Sensitization prior to transplant can occur by pregnancy or blood transfusions. Previous transplantation can also sensitize patients against HLA molecules. Blood transfusions can induce humoral immunity by formation of HLA alloantibodies and are more likely to occur in individuals who have been previously pregnant. Our understanding of how blood transfusions cause sensitization is incomplete, but it is not inevitable and can be attenuated by immunosuppression. In a study
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