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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 21, 2015; 21(39): 11016-11026
Published online Oct 21, 2015. doi: 10.3748/wjg.v21.i39.11016
Clinical significance of donor-specific human leukocyte antigen antibodies in liver transplantation
Antonio Cuadrado, David San Segundo, Marcos López-Hoyos, Javier Crespo, Emilio Fábrega
Antonio Cuadrado, Javier Crespo, Emilio Fábrega, Gastroenterology and Hepatology Unit, Marqués de Valdecilla University Hospital, Instituto de Investigación Marqués de Valdecilla, 39008 Santander, Cantabria, Spain
David San Segundo, Marcos López-Hoyos, Immunology Unit, Marqués de Valdecilla University Hospital. Instituto de Investigación Marqués de Valdecilla, 39008 Santander, Cantabria, Spain
Author contributions: Cuadrado A, San Segundo D, López-Hoyos M, Crespo J and Fábrega E analyzed the literature and wrote the manuscript.
Conflict-of-interest statement: The authors have no conflict of interest to report.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Emilio Fábrega, MD, PhD, Gastroenterology and Hepatology Unit, Marqués de Valdecilla University Hospital, Avenida Valdecilla s/n, 39008 Santander, Cantabria. Spain. digfge@humv.es
Telephone: +34-73-442202544 Fax: +34-73-442202544
Received: April 18, 2015
Peer-review started: April 19, 2015
First decision: June 23, 2015
Revised: June 29, 2015
Accepted: September 13, 2015
Article in press: September 13, 2015
Published online: October 21, 2015
Abstract

Antibody-mediated rejection (AMR) caused by donor-specific anti-human leukocyte antigen antibodies (DSA) is widely accepted to be a risk factor for decreased graft survival after kidney transplantation. This entity also plays a pathogenic role in other solid organ transplants as it appears to be an increasingly common cause of heart graft dysfunction and an emerging issue in lung transplantation. In contrast, the liver appears relatively resistant to DSA-mediated injury. This “immune-tolerance” liver property has been sustained by a low rate of liver graft loss in patients with preformed DSA and by the intrinsic liver characteristics that favor the absorption and elimination of DSA; however, alloantibody-mediated adverse consequences are increasingly being recognized, and several cases of acute AMR after ABO-compatible liver transplant (LT) have been reported. Furthermore, the availability of new solid-phase assays, allowing the detection of low titers of DSA and the refinement of objective diagnostic criteria for AMR in solid organ transplants and particularly in LT, have improved the recognition and management of this entity. A cost-effective strategy of DSA monitoring, avoidance of class II human leukocyte antigen mismatching, judicious immunosuppression attached to a higher level of clinical suspicion of AMR, particularly in cases unresponsive to conventional anti-rejection therapy, can allow a rational approach to this threat.

Keywords: Donor-specific anti-human leukocyte antigen antibodies, Liver transplantation, Rejection, Acute antibody-mediated rejection, C4d, Solid-phase immunoassays, Human leukocyte antigen single antigen bead

Core tip: The role of donor-specific anti-human leukocyte antigen antibodies (DSA) in liver transplant (LT) remains unclear. Alloantibody-mediated adverse consequences are increasingly being recognized, and several cases of acute antibody-mediated rejection after ABO-compatible LT have been reported. There is a need to investigate and quantify the potential adverse impact of DSA on LT outcomes. The present review addresses the current knowledge on this issue.