Skip to Main content Skip to Navigation

Rôle pronostic des anticorps anti-HLA en transplantation rénale : approches en population

Abstract : Background : The alloimmune response induced by transplantation from a donor who differs genetically from the kidney recipient has always been the major obstacle to graft success. The present work aimed to improve characterization of kidney-allograft rejection phenotypes and identify how each one is associated with anti-HLA antibodies. We also sought to determine whether characteristics of these antibodies i.e., their levels or complementbinding ability, might play a role in kidney allograft failure. Finally, we evaluated the clinical relevance of indolent forms of ABMR and the clinical relevance of new genes expression technologies to stratify the kidney recipients at risk for failure. Methods : We used a population-based approach in precisely phenotyped cohorts of kidney recipients. The design of our study, which is based on the concomitant evaluation of immunologic and histologic data, permits a precise connection of circulating anti-HLA antibodies with a phenotype of graft injury. Findings : We identified four distinct patterns of kidney allograft rejection: T cell-mediated vascular rejection (9%), antibody-mediated vascular rejection (21%), not included in international classifications, T cell- (46%) and antibody-mediated rejection without vasculitis (24%). Risk of graft loss was 9.07 times (95CI 3.6-19.7) higher in antibody-mediated vascular rejection than in T-cell mediated rejections (p<0.0001). Patients with post-transplant complement-binding DSA had more severe graft injury phenotype with higher inflammation and increased deposition of complement fraction C4d. They have the poorest graft survival with 3.7 fold increased risk of graft loss (95CI 1.9-7.2). Subclinical ABMR is a truncated for of rejection associated with risk of kidney allograft failure. Gene expression assessment in kidney allografts with early ABMR improves classification of individuals at risk for kidney allograft loss. Conclusion : This work addresses the unmet need of the deleterious impact of anti-HLA antibodies and the improvement of risk stratification in kidney transplantation. Recognition of distinct phenotypes could lead to the development of new treatment strategies. Gene expression assessment appears useful to evaluate disease activity, disease state and prediction of failure.
Document type :
Theses
Complete list of metadatas

Cited literature [128 references]  Display  Hide  Download

https://tel.archives-ouvertes.fr/tel-01195994
Contributor : Abes Star :  Contact
Submitted on : Tuesday, September 8, 2015 - 6:36:06 PM
Last modification on : Friday, March 27, 2020 - 2:33:24 AM
Document(s) archivé(s) le : Wednesday, December 9, 2015 - 11:28:33 AM

File

vd_Loupy_Alexandre.pdf
Version validated by the jury (STAR)

Identifiers

  • HAL Id : tel-01195994, version 1

Collections

Citation

Alexandre Loupy. Rôle pronostic des anticorps anti-HLA en transplantation rénale : approches en population. Médecine humaine et pathologie. Université René Descartes - Paris V, 2014. Français. ⟨NNT : 2014PA05S005⟩. ⟨tel-01195994⟩

Share

Metrics

Record views

380

Files downloads

3929