Editorial
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 7, 2023; 29(5): 766-772
Published online Feb 7, 2023. doi: 10.3748/wjg.v29.i5.766
Importance of human leukocyte antigen antibodies and leukocyte antigen/killer-cell immunoglobulin-like receptor genes in liver transplantation
Manuel Muro, Isabel Legaz
Manuel Muro, Immunology Service, University Clinical Hospital Virgen de la Arrixaca-Biomedical Research Institute of Murcia (IMIB), Murcia 30120, Spain
Isabel Legaz, Department of Legal and Forensic Medicine, Biomedical Research Institute (IMIB), Regional Campus of International Excellence “Campus Mare Nostrum,” Faculty of Medicine, University of Murcia, Murcia 30120, Spain
Author contributions: Muro M and Legaz I equally participated in the writing and review of the manuscript.
Supported by Instituto de Salud Carlos III, Spanish Ministry of Economy and Competitiveness, No. PI15/01370 and P19/01194; and the European Union with the European Fund of Regional Development with the principle of “A manner to build Europe”.
Conflict-of-interest statement: The authors have no relevant conflicts of interest to disclose.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Manuel Muro, PhD, Senior Researcher, Immunology Service, University Clinical Hospital Virgen de la Arrixaca-Biomedical Research Institute of Murcia (IMIB), El Palmar, Murcia 30120, Spain. manuel.muro@carm.es
Received: September 7, 2022
Peer-review started: September 7, 2022
First decision: October 19, 2022
Revised: October 25, 2022
Accepted: January 17, 2023
Article in press: January 17, 2023
Published online: February 7, 2023
Processing time: 152 Days and 3.7 Hours
Abstract

Many mechanisms have been proposed to explain the hypothetical state of hepatic tolerance, which is described by eventual imbalances or deregulation in the balance of cytokines, mediators, effectors, and regulatory cells in the complex milieu of the liver. In this section, we will comment on the importance of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) as well as the compatibility and pairings of HLA and killer-cell immunoglobulin-like receptor (KIR) genotypes in the evolution of liver transplantation. Thus, HLA compatibility, viral infections, and HLA-C/KIR combinations have all been linked to liver transplant rejection and survival. There have been reports of increased risk of acute and chronic rejection with ductopenia, faster graft fibrosis, biliary problems, poorer survival, and even de novo autoimmune hepatitis when DSAs are present in the recipient. Higher mean fluorescence intensity (MFI) values of the DSAs and smaller graft size were associated with poorer patient outcomes, implying that high-risk patients with preformed DSAs should be considered for selecting the graft placed and desensitization methods, according to the investigators. Similarly, in a combined kidney-liver transplant, a pretransplant with a visible expression of several DSAs revealed that these antibodies were resistant to treatment. The renal graft was lost owing to antibody-mediated rejection (AMR). The HLA antigens expressed by the transplanted liver graft influenced antibody elimination. Pathologists are increasingly diagnosing AMR in liver transplants, and desensitization therapy has even been employed in situations of AMR, particularly in patients with DSAs in kidney-hepatic transplants and high-class II MFI due to Luminex. In conclusion, after revealing the negative impacts of DSAs with high MFI, pretransplant virtual crossmatch techniques may be appropriate to improve evolution; however, they may extend cold ischemia periods by requiring the donor to be typed.

Keywords: Acute rejection; Alloantibodies donor-specific antibodies-donor-specific anti-human leukocyte antigen antibodies; Chronic rejection; Human leukocyte antigen matching; Killer-cell immunoglobulin-like receptor matching; Liver transplant

Core Tip: This editorial aimed to raise realities, doubts, and ambiguities in the fundamental role of alloantibodies and the compatibility and association of the proteins encoded by the human leukocyte antigen and killer-cell immunoglobulin-like receptor genes in liver transplantation.