Antibody‐Mediated Rejection in Kidney Transplantation: A Review of Pathophysiology, Diagnosis, and Treatment Options

Abstract

Antibody-mediated rejection (AMR), also known as B-cell-mediated or humoral rejection, is a significant complication after kidney transplantation that carries a poor prognosis. Although fewer than 10% of kidney transplant patients experience AMR, as many as 30% of these patients experience graft loss as a consequence. Although AMR is mediated by antibodies against an allograft and results in histologic changes in allograft vasculature that differ from cellular rejection, it has not been recognized as a separate disease process until recently. With an improved understanding about the importance of the development of antibodies against allografts as well as complement activation, significant advances have occurred in the treatment of AMR. The standard of care for AMR includes plasmapheresis and intravenous immunoglobulin that remove and neutralize antibodies, respectively. Agents targeting B cells (rituximab and alemtuzumab), plasma cells (bortezomib), and the complement system (eculizumab) have also been used successfully to treat AMR in kidney transplant recipients. However, the high cost of these medications, their use for unlabeled indications, and a lack of prospective studies evaluating their efficacy and safety limit the routine use of these agents in the treatment of AMR in kidney transplant recipients.

Immune response to enzyme replacement therapies in lysosomal storage diseases and the role of immune tolerance induction

“…of multiple myeloma, a plasma cell tumor, and has also been used for kidney transplant rejection with some success [54].…”

Antibody-mediated rejection: New approaches in prevention and management

“…Antibody-secreting plasma cells do not express CD20 and would not be expected to have any response to anti-CD20. 48 One systematic review and meta-analysis of 10 small retrospective or nonrandomized trials evaluating use of rituximab in AMR suggested that use of this agent is associated with improved graft outcome; however, the favorable effect was driven by 2 larger studies included in the analysis. 49 A systematic review of 21 studies (2 randomized controlled trials and 19 retrospective cohort studies) did not support the use of rituximab in desensitization in highly sensitized recipients.…”

Inmunosupresores y principales complicaciones en el trasplante renal pediátrico

“…En ambas vías de alorreconocimiento están implicados el complejo mayor de histocompatibilidad (CMH), los distintos subgrupos de células T (TH1 y TH2) y la coestimulación (45,49). Los anticuerpos que pueden mediar el rechazo de tipo humoral son aquellos dirigidos contra moléculas HLA, antígenos de la célula endotelial y antígenos del complejo ABO en células endoteliales y eritrocitos (50). Generalmente, el rechazo humoral (o rechazo mediado por anticuerpos) se manifiesta como hiperagudo o agudo, en pacientes presensibilizados; sucede en el postrasplante temprano o en pacientes que desarrollan anticuerpos donante-específicos en el período del postrasplante tardío (51).…”