title: Humoral theory of transplantation: mechanism, prevention, and treatment.
abstract: We discuss the potential mechanisms of antibody-induced primary endothelium injury, which includes complement-dependent pathway (membrane attack complex formation, recruitment of inflammatory cells, and complement-complement receptor-mediated phagocytosis) and complement independent pathway antibody-dependent cell cytotoxicity. Secondary to endothelium injury, the following pathological reactions are found to be responsible for progressive tissue injury and final graft function loss: platelet activation and thrombosis, pathological smooth muscle and endothelial cell proliferation, and humoral and/or cellular infiltrate-mediated parenchyma damage after endothelium injury. We also introduce three categories of therapeutic strategy in the prevention and treatment of antibody-mediated rejection: (1) inhibition and depletion of antibody producing cells (immunosuppressants, antilymphocyte antibodies, splenectomy); (2) removal or blockage of preexisting or newly developed antibodies (immunoadsorption, plasmapheresis/plasma exchange, intravenous immunoglobulin); and (3) impediment or postponement of antibody-mediated primary and secondary tissue injury (anticoagulation, glucosteroids). In conclusion, because alloantibodies have destructive effect on allografts, alloantibody monitoring becomes extremely important. It will help clinicians to determine a patient's humoral responses against allograft and will therefore direct clinicians to optimize and/or minimize immunosuppressive drug therapy.
authors.affiliation: Terasaki Foundation Laboratory, Los Angeles, CA 90064, USA.
authors.forename: Junchao
authors.initials: J
authors.lastname: Cai
authors.forename: Paul I
authors.initials: PI
authors.lastname: Terasaki
mesh_terms: D000818:Animals; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy*; D006801:Humans; D007518:Isoantibodies / Q000009:adverse effects* / Q000096:biosynthesis* / Q000502:physiology
chemical_list: D007518:Isoantibodies