Background
Epitope-based tissue matching may be superior to HLA antigen matching. We compared
antigen to molecular-level HLA matching on outcomes following pediatric heart transplantation
(HTx).
Methods
This is a retrospective, single centre cohort study (2013-2020). HLA antigen and eplet
mismatch analyses were performed in HTx patients <18 years old. Primary endpoint was
graft loss; secondary endpoints were rejection and cardiac allograft vasculopathy
(CAV). A multivariable Cox regression analysis was used to examine associations between
eplet or antigen mismatching and outcomes. A logistic regression analysis was performed
to examine associations between eplet or antigen mismatching and outcomes.
Results
Seventy-seven patients (40% males) were included, with a median age at HTx 4.3 years
[range 0.05-18]. Median HLA class I and II eplet mismatches were 10 (1-22) and 11
(1-23). Median class I and II antigen mismatches were 5 (1-6) and 4 (0-6). 9 patients
(11.7%) died [median time 4 months (range 0.1-46)]. Eight (10.4%) patients developed
AMR [median time 22 days (IQR = 168)]. Twenty-one patients (27.3%) had acute cellular
rejection [median time 40 days (IQR = 85.5)]. In univariate analysis, patients with
HLA Class II DPB eplet mismatches above the median for this cohort had an increased
risk of graft loss (OR 5.3 [95%CI: 1.03-27.5], p = 0.039). HLA eplet mismatching was not associated with rejection; antigen mismatching
was not associated with either graft loss or rejection. In multivariable analysis,
patients with HLA Class II DPB eplet mismatches above the median had an increased
risk of graft loss (HR 8.14 [95% CI: 1.26-49], p = 0.02). HLA eplet mismatching was not associated with rejection; antigen mismatching
was not associated with graft loss or rejection. A logistic regression analysis including
'number of HLA Class II DPB eplet mismatches’ correctly predicted 95.8% of the outcomes.
Conclusion
In our cohort of pediatric heart transplant recipients, the number of HLA Class II
DPB eplet mismatches was associated with graft loss. Molecular-level HLA matching
is an emerging tool for graft loss risk stratification, but further study is required.
KEYWORDS
Abbreviations:
ABOi (ABO-incompatible), ACR (acute cellular rejection), AMR (antibody mediated rejection), CAV (cardiac allograft vasculopathy), CHD (congenital heart disease), cPRA (calculated panel reactive antibody), dnDSA (de novo donor specific antibodies), ECMO (extracorporeal membrane oxygenation), HLA (human leukocyte antigen), ISHLT (International Society for Heart and Lung Transplantation)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to The Journal of Heart and Lung TransplantationAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- HLA epitope matching in pediatric renal transplantation.Pediatr Nephrol. 2017; 32: 1861-1869https://doi.org/10.1007/s00467-016-3557-4
- Molecular-level HLA mismatch is associated with rejection and worsened graft survival in heart transplant recipients – a retrospective study.Transpl Int. 2020; 33: 1078-1088https://doi.org/10.1111/tri.13657
- Association of human leukocyte antigen donor-recipient matching and pediatric heart transplant graft survival.Circ Hear Fail. 2014; 7: 605-611https://doi.org/10.1161/CIRCHEARTFAILURE.113.001008
- HLA molecular epitope mismatching and long-term graft loss in pediatric heart transplant recipients.J Hear Lung Transplant. 2015; 34: 950-957https://doi.org/10.1016/j.healun.2014.12.017
- Human leukocyte antigen-based risk stratification in heart transplant recipients—implications for targeted surveillance.J Am Heart Assoc. 2019; 8: 1-12https://doi.org/10.1161/JAHA.118.011124
- Class II eplet mismatch modulates tacrolimus trough levels required to prevent donor-specific antibody development.J Am Soc Nephrol. 2017; 28: 3353-3362https://doi.org/10.1681/ASN.2017030287
- More precise donor-recipient matching: the role of eplet matching.Curr Opin Nephrol Hypertens. 2020; 29: 630-635https://doi.org/10.1097/MNH.0000000000000649
- Towards the identification of the relative immunogenicity of individual HLA antibody epitopes.Hum Immunol. 2019; 80: 218-220https://doi.org/10.1016/j.humimm.2019.02.002
- Differences in immunogenicity of HLA antigens and the impact of cross-reactivity on the humoral response.Transplantation. 2015; 99: 77-85https://doi.org/10.1097/TP.0000000000000355
- The 2013 international society for heart and lung transplantation working formulation for the standardization of nomenclature in the pathologic diagnosis of antibody-mediated rejection in heart transplantation.J Hear Lung Transplant. 2013; 32: 1147-1162https://doi.org/10.1016/j.healun.2013.08.011
- Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection.J Hear lung Transplant Off Publ Int Soc Hear Transplant. 2005; 24: 1710-1720https://doi.org/10.1016/j.healun.2005.03.019
- International Society for Heart and Lung Transplantation working formulation of a standardized nomenclature for cardiac allograft vasculopathy-2010.J Hear Lung Transplant. 2010; 29: 717-727https://doi.org/10.1016/j.healun.2010.05.017
- 16th IHIW: a website for antibody-defined HLA epitope registry.Int J Immunogenet. 2013; 40: 54-59https://doi.org/10.1111/iji.12017
- Application of an epitope-based allocation system in pediatric kidney transplantation.Pediatr Transplant. 2016; 20: 931-938https://doi.org/10.1111/petr.12815
- Predictive value of HLAMatchmaker and PIRCHE-II scores for de novo donor-specific antibody formation after adult and pediatric liver transplantation.Transpl Immunol. 2020; 61101306https://doi.org/10.1016/j.trim.2020.101306
- The association between human leukocyte antigen eplet mismatches, de novo donor-specific antibodies, and the risk of acute rejection in pediatric kidney transplant recipients.Pediatr Nephrol. 2020; 35: 1061-1068https://doi.org/10.1007/s00467-020-04474-x
- Human leukocyte antigen eplet mismatching is associated with increased risk of graft loss and rejection after pediatric heart transplant.Pediatr Transplant. 2021; 26: e14126
- Class II HLA eplet mismatch is a risk factor for de novo donor-specific antibody development and antibody-mediated rejection in kidney transplantation recipients.in: Transplantation Proceedings. 50. 2018: 2388-2391 (Elsevier)
- Class II human leukocyte antigen epitope mismatch predicts de novo donor-specific antibody formation after liver transplantation.Liver Transplant. 2018; 24: 1101-1108
- Identification of risk epitope mismatches associated with de novo donor-specific HLA antibody development in cardiothoracic transplantation.Am J Transplant. 2018; 18: 2924-2933https://doi.org/10.1111/ajt.14951
- HLA-DQ mismatches stimulate de novo donor specific antibodies in heart transplant recipients.Hum Immunol. 2020; 81: 330-336https://doi.org/10.1016/j.humimm.2020.04.003
- De novo DQ donor-specific antibodies are associated with a significant risk of antibody-mediated rejection and transplant glomerulopathy.Transplantation. 2012; 94: 172-177
- HLA-DQ mismatches and rejection in kidney transplant recipients.Clin J Am Soc Nephrol. 2016; 11: 875-883
- Eplet-based HLA class II matching for transplantation: design of a repertoire of interlocus eplets shared between HLA-DR, -DQ and -DP alleles.OBM Transplant. 2020; 4https://doi.org/10.21926/obm.transplant.2001099
- HLA-epitope matching or eplet risk stratification: the devil is in the details.Front Immunol. 2018; 9: 2010https://doi.org/10.3389/fimmu.2018.02010
Article info
Publication history
Published online: July 05, 2022
Identification
Copyright
© 2022 International Society for Heart and Lung Transplantation. All rights reserved.
ScienceDirect
Access this article on ScienceDirectRelated Articles
Related Podcast
JHLT: The Podcast Episode 22: October 2022
For this month’s episode, JHLT The Podcast explores two impactful studies from the October issue of The Journal of Heart and Lung Transplantation. The episode is hosted by Daniel R. Goldstein, MD, Editor-in-Chief of JHLT, who is joined by the JHLT Digital Media Editors. Listen now to hear study authors discuss their work, their studies, and next steps for their research.
First, the editors speak with first author Michael Harhay, PhD (pictured left) and senior author Edward Cantu, MD (pictured right), about their study from the University of Pennsylvania entitled “Epidemiology, risk factors and outcomes of lung retransplantation: an analysis of the ISHLT Transplant Registry.” Dr. Goldstein and Erika Lease, MD, interview Drs. Harhay and Cantu about the study.
The objective of the study was to leverage the ISHLT Thoracic Transplant registry using an updated cohort of patients that underwent lung retransplantation to obtain an updated summary of the epidemiology of lung retransplantation; to examine the importance of the time between primary transplantation and retransplantation on outcomes after retransplantation; and to identify risk factors of mortality following lung retransplantation.
