Copyright
©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
Human leukocyte antigen compatibility and incidence of donor-specific antibodies in pediatric liver transplant recipients
Melina U Melere, Flavia H Feier, Jorge Neumann, Antônio N Kalil, Juliana de M Montagner, Luiza S Nader, Carolina S da Silva, Marco Aurélio F Junior, Gabriela P Coral, Guilherme P Bobsin, Cristina T Ferreira
Melina U Melere, Luiza S Nader, Carolina S da Silva, Marco Aurélio F Junior, Gabriela P Coral, Guilherme P Bobsin, Cristina T Ferreira, Department of Hepatology and Liver Transplantation, Santa Casa de Porto Alegre, Porto Alegre 90050170, Rio Grande do Sul, Brazil
Flavia H Feier, Antônio N Kalil, Department of Hepato-biliary-pancreatic Surgery and Liver Transplantation, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90020-090, Rio Grande do Sul, Brazil
Flavia H Feier, Antônio N Kalil, Gabriela P Coral, Postgraduation Program in Medicine: Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Rio Grande do Sul, Brazil
Jorge Neumann, Juliana de M Montagner, Laboratory of Transplantation Immunology, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90020-090, Rio Grande do Sul, Brazil
Author contributions: Melere MU, Feier FH, and Neumann J designed the research study and wrote the manuscript; Nader LS, Junior MAF, da Silva CS, Montagner JM, Coral GP, and Bobsin GP collected and evaluated the data; Ferreira CT and Kalil AN wrote the manuscript and critically evaluated the final version. All authors have read and approved the final manuscript.
Institutional review board statement: This study was approved by the Ethics and Research Committee of the Federal University of Health Sciences of Porto Alegre (UFCSPA) and the Santa Casa de Misericórdia de Porto Alegre Complex (ISCMPA) (approval numbers 3805918 and 3938979, respectively). This study was also registered at the Brazilian Clinical Trials Registry (ReBec) under number RBR-3 gtcvjU111112367585.
Informed consent statement: Upon signing the informed consent form for LT, the patients also provided signed authorization for sample collection.
Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript.
Data sharing statement: The original anonymous dataset is available on request from the corresponding author at
flavia.feier@gmail.com.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
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: Flavia H Feier, PhD, Professor, Department of Hepato-biliary-pancreatic Surgery and Liver Transplantation, Irmandade Santa Casa de Misericórdia de Porto Alegre, Rua Prof Annes Dias, Porto Alegre 90020-090, Rio Grande do Sul, Brazil.
flavia.feier@gmail.com
Received: May 9, 2024
Revised: August 1, 2024
Accepted: August 20, 2024
Published online: September 7, 2024
Processing time: 115 Days and 8.2 Hours
BACKGROUND
Antibody-mediated rejection following liver transplantation (LT) has been increasingly recognized, particularly with respect to the emergence of de novo donor-specific antibodies (DSAs) and their impact on graft longevity. While substantial evidence for adult populations exists, research focusing on pediatric LT outcomes remains limited.
AIM
To investigate the prevalence of human leukocyte antigen (HLA) mismatches and DSA and evaluate their association with rejection episodes after pediatric LT.
METHODS
A cohort of pediatric LT recipients underwent HLA testing at Santa Casa de Porto Alegre, Brazil, between December 2013 and December 2023. Only patients who survived for > 30 days after LT with at least one DSA analysis were included. DSA classes I and II and cross-matches were analyzed. The presence of de novo DSA (dnDSA) was evaluated at least 3 months after LT using the Luminex® single antigen bead method, with a positive reaction threshold set at 1000 MFI. Rejection episodes were confirmed by liver biopsy.
RESULTS
Overall, 67 transplanted children were analyzed; 61 received grafts from living donors, 85% of whom were related to recipients. Pre-transplant DSA (class I or II) was detected in 28.3% of patients, and dnDSA was detected in 48.4%. The median time to DSA detection after LT was 19.7 [interquartile range (IQR): 4.3-35.6] months. Biopsy-proven rejection occurred in 13 patients at follow-up, with C4d positivity observed in 5/13 Liver biopsies. The median time to rejection was 7.8 (IQR: 5.7-12.8) months. The presence of dnDSA was significantly associated with rejection (36% vs 3%, P < 0.001). The rejection-free survival rates at 12 and 24 months were 76% vs 100% and 58% vs 95% for patients with dnDSA anti-DQ vs those without, respectively.
CONCLUSION
Our findings highlight the importance of incorporating DSA assessment into pre- and post-transplantation protocols for pediatric LT recipients. Future implications may include immunosuppression minimization strategies based on this analysis in pediatric LT recipients.
Core Tip: The assessment of human leucocyte antigens and donor-specific antibodies (DSAs) is becoming crucial in pediatric liver transplantation (LT). This cohort study demonstrates the association of DSAs with rejection episodes after LT.
