Journal Article Ppublish
PubMed: 40667760 DOI: 10.1111/tan.70320
Donor HLA Class I Evolutionary Divergence and Late Allograft Rejection After Liver Transplantation in Children: An Emulated Target Trial.
HLA 106(1):e70320
Authors: Jérôme Dumortier, Sarah Hamada, Emma Wischlen, Céline Mandier, Noémie Laverdure, Olivier Boillot, Ilias Kounis, Vincent Allain, Valérie Hervieu, Sophie Collardeau-Frachon, Valérie Dubois, Cyrille Feray
Affiliations
- Hospices Civils de Lyon, Hôpital Edouard Herriot, Fédération Des Spécialités Digestives, Lyon, France.
- Université Claude Bernard Lyon 1, Lyon, France.
- Etablissement Français du Sang, Décines, France.
- Hospices Civils de Lyon, Hôpital Femme-Mère-Enfants, Service d'Hépato-Gastroentérologie et Nutrition, Bron, France.
- AP-HP, Hôpital Paul Brousse, Centre Hépato-Biliaire, INSERM, Unité 1193, Hepatinov, and Université Paris-Saclay, Villejuif, France.
- Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Université de Paris, Laboratoire d'Immunologie et Histocompatibilité, Paris, France.
- Hospices Civils de Lyon, Groupe Hospitalier Est, Service d'Anatomie Pathologique, Bron, France.
Abstract
HLA evolutionary divergence (HED), a continuous metric quantifying the differences between each amino acid of two homologous HLA alleles, reflects the importance of the immunopeptidome presented to T lymphocytes. It has been associated with rejection after liver transplantation. This retrospective cohort study aimed to analyse the potential effect of donor or recipient HED on liver transplant rejection in a new series of patients transplanted during childhood and followed in adulthood. The study included 120 children who had been transplanted between 1991 and 2010 and were followed by routine biopsies and histological evaluations with a median of 14.1 years post-LT. Liver biopsies were performed routinely 1, 5, 10 and 20 years after transplantation and in the event of liver dysfunction. HED was calculated using the physicochemical Grantham distance for donor and recipient Class I (HLA-A, -B, -C) and Class II (HLA-DRB1, -DQB1) alleles. The influence of HED on rejection was analysed using inverse probability weighting (IPW) and target trial emulation using the g method. Based on the IPW score, donor HED class I was correlated with the occurrence of late (> 90 days) rejection (HR, 1.19, 95% CI: 1.01-1.40) independently of HLA mismatches, donor age and initial induction. The emulated target trial confirmed that donor HED Class I has a causal effect on liver graft rejection and this relationship was observed long-term.
MeSH
Graft Rejection, Liver Transplantation, Biopsy, Liver, Hla Antigens, Alleles, Transplants, Allografts, Transplantation, Child