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Article Dans Une Revue The Journal of Heart and Lung Transplantation Année : 2023

Chronic lung allograft dysfunction is associated with an increased number of non-HLA antibodies

Qingyong Xu
Mohamed Elrefaei
Jean-Luc Taupin
  • Fonction : Auteur
Kelley M.K. Hitchman
  • Fonction : Auteur
Steven Hiho
  • Fonction : Auteur
Alison Gareau
Carlo Iasella
  • Fonction : Auteur
Marilyn Marrari
  • Fonction : Auteur
Natalia Belousova
Maria Bettinotti
Tathagat Narula
Francisco Alvarez
  • Fonction : Auteur
Pablo Sanchez
  • Fonction : Auteur
Bronwyn Levvey
Glen Westall
Gregory Snell
  • Fonction : Auteur
Deborah Levine
  • Fonction : Auteur
Adriana Zeevi
  • Fonction : Auteur

Résumé

Background: Chronic lung allograft dysfunction (CLAD) is the major cause of adverse outcomes in lung transplant recipients. Multiple factors, such as infection, alloimmunity, and autoimmunity, may lead to CLAD. Here, we aim to examine the role of non-human leukocytes antigen (HLA) antibodies in CLAD in a large retrospective cohort. Methods: We analyzed non-HLA antibodies in the pre- and post-transplant sera of 226 (100 CLAD, 126 stable) lung transplant recipients from 5 centers, and we used a separate cohort to confirm our findings. Results: A panel of 18 non-HLA antibodies was selected for analysis based on their significantly higher positive rates in CLAD vs stable groups. The panel-18 non-HLA antibodies (n > 3) may be positive pre- or post-transplant; the risk for CLAD is higher in the latter. The presence of both non-HLA antibody and HLA donor-specific antibody (DSA) was associated with an augmented risk of CLAD (HR=25.09 [5.52-14.04], p < 0.001), which was higher than that for single-positive patients. In the independent confirmatory cohort of 61 (20 CLAD, 41 stable) lung transplant recipients, the risk for CLAD remained elevated in double-positive patients (HR=10.67 [0.98-115.68], p = 0.052). After adjusting for nonstandard immunosuppression, patients with double-positive DSA/Non-HLA antibodies had an elevated risk for graft loss (HR=2.53 [1.29-4.96], p = 0.007). Conclusions: Circulating non-HLA antibodies (n > 3) were independently associated with a higher risk for CLAD. Furthermore, when non-HLA antibodies and DSA were detected concomitantly, the risk for CLAD and graft loss was significantly increased. These results show that humoral immunity to HLA and non-HLA antigens may contribute to CLAD development. Keywords: HLA; chronic lung allograft dysfunction; donor-specific antibody; lung; non-HLA antibody; transplantation. Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
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Dates et versions

hal-04473049 , version 1 (22-02-2024)

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Qingyong Xu, Mohamed Elrefaei, Jean-Luc Taupin, Kelley M.K. Hitchman, Steven Hiho, et al.. Chronic lung allograft dysfunction is associated with an increased number of non-HLA antibodies. The Journal of Heart and Lung Transplantation, 2023, ⟨10.1016/j.healun.2023.12.007⟩. ⟨hal-04473049⟩
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