Editorial
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World J Transplant. Mar 24, 2014; 4(1): 1-17
Published online Mar 24, 2014. doi: 10.5500/wjt.v4.i1.1
Impact of donor-specific antibodies on the outcomes of kidney graft: Pathophysiology, clinical, therapy
Maurizio Salvadori, Elisabetta Bertoni
Maurizio Salvadori, Elisabetta Bertoni, Department of Renal Transplantation, Careggi University Hospital, 50139 Florence, Italy
Author contributions: Salvadori M and Bertoni E contributed equally to the concept, acquisition of data, drafting of the article, revisions and final approvals.
Correspondence to: Maurizio Salvadori, MD, Department of Transplantation, Careggi University Hospital, viale Pieraccini 18, 50139 Florence, Italy. maurizio.salvadori1@gmail.com
Telephone: +39-55-597151 Fax: +39-55-597151
Received: November 1, 2013
Revised: January 23, 2014
Accepted: March 3, 2014
Published online: March 24, 2014
Processing time: 103 Days and 19.2 Hours
Abstract

Allo-antibodies, particularly when donor specific, are one of the most important factors that cause both early and late graft dysfunction. The authors review the current state of the art concerning this important issue in renal transplantation. Many antibodies have been recognized as mediators of renal injury. In particular donor-specific-Human Leukocyte Antigens antibodies appear to play a major role. New techniques, such as solid phase techniques and Luminex, have revealed these antibodies from patient sera. Other new techniques have uncovered alloantibodies and signs of complement activation in renal biopsy specimens. It has been acknowledged that the old concept of chronic renal injury caused by calcineurine inhibitors toxicity should be replaced in many cases by alloantibodies acting against the graft. In addition, the number of patients on waiting lists with preformed anti-human leukocyte antigens (HLA) antibodies is increasing, primarily from patients with a history of renal transplant failure already been sensitized. We should distinguish early and late acute antibody-mediated rejection from chronic antibody-mediated rejection. The latter often manifets late during the course of the post-transplant period and may be difficult to recognize if specific techniques are not applied. Different therapeutic strategies are used to control antibody-induced damage. These strategies may be applied prior to transplantation or, in the case of acute antibody-mediated rejection, after transplantation. Many new drugs are appearing at the horizon; however, these drugs are far from the clinic because they are in phase I-II of clinical trials. Thus the pipeline for the near future appears almost empty.

Keywords: Donor-specific antibodies; Solid-phase techniques; Complement activation; Renal transplantation; Antibody-mediated rejection; Desensitization; New drugs for B-cells

Core tip: Clear evidence exists that shows that donor-specific-HLA antibodies (DSAs) are the primary players in the acute and chronic deterioration of graft. The emergence of sensitive techniques that detect DSAs, together with advances in the assessment of graft pathology, has enabled an improved understanding of antibody-mediated graft injury. Acute and chronic antibody-mediated rejection conditions have changed the nomenclature during recent Banff conferences and have enabled the dismissal of older terminologies, such as chronic allograft nephropathy. Therapies aimed at B cells and plasma cells and that control complement activation will be extremely important for improving long-term outcomes in kidney transplantations.