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Journal Article
Research Support, Non-U.S. Gov't
Review
Antibody-mediated rejection: treatment alternatives and outcomes.
Transplantation Reviews 2009 January
Over the past 10 years, thanks to the development of sensitive methods of antibody detection and markers of antibody injury such as C4d staining, the role of anti-human leukocyte antigen (HLA) and non-HLA alloantibodies as effectors of acute and chronic immune allograft injury has been revisited. Antibody-mediated rejection (AMR) defines all allograft rejection caused by antibodies directed against donor-specific HLA molecules, blood group antigen (ABO)-isoagglutinins, or endothelial cell antigens. Antibody-mediated rejection can be a recalcitrant process, resistant to therapy and carries an ominous prognosis to the graft. In concordance with these views, treatment protocols for AMR use permutations of a multiple-prong approach that include (1) the suppression of the T-cell dependent antibody response, (2) the removal of donor reactive antibody, (3) the blockade of the residual alloantibody, and (4) the depletion of naive and memory B-cells. Although all published protocols report a variable rate of success, a major weakness of all current protocols is the lack of effective anti-plasma cell agents. In comparison to acute AMR, the treatment for chronic AMR (CAMR) is not well characterized. Although in acute AMR large titers of pre-existent alloantibodies result in massive activation of the complement system and lytic injury of the graft endothelium, thereby requiring aggressive and fast removal of the offending agents, in CAMR, complement activation results in sublytic endothelial cell injury and activation. Although this type of injury results in chronic graft failure, its slow progression likely renders it amenable of suppression by heightening of maintenance immunosuppression and anti-idiotypic blockade of the circulating alloantibody without the need of plasma exchange. In this review, we will discuss the rationale behind the design of treatment protocols for acute AMR and CAMR as well as their reported results and complications.
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