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© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Antibody-mediated rejection (ABMR) is the leading cause of allograft failure in kidney transplantation. Its histological hallmark is represented by lesions of glomerulitis i.e., inflammatory cells within glomeruli. Current therapies for ABMR fail to prevent chronic allograft damage i.e., transplant glomerulopathy, leading to allograft loss. We used laser microdissection of glomeruli from formalin-fixed allograft biopsies combined with mass spectrometry-based proteomics to describe the proteome modification of 11 active and 10 chronic active ABMR cases compared to 8 stable graft controls. Of 1335 detected proteins, 77 were deregulated in glomerulitis compared to stable grafts, particularly involved in cellular stress mediated by interferons type I and II, leukocyte activation and microcirculation remodeling. Three proteins extracted from this protein profile, TYMP, WARS1 and GBP1, showed a consistent overexpression by immunohistochemistry in glomerular endothelial cells that may represent relevant markers of endothelial stress during active ABMR. In transplant glomerulopathy, 137 proteins were deregulated, which favor a complement-mediated mechanism, wound healing processes through coagulation activation and ultimately a remodeling of the glomerular extracellular matrix, as observed by light microscopy. This study brings novel information on glomerular proteomics of ABMR in kidney transplantation, and highlights potential targets of diagnostic and therapeutic interest.

Details

Title
The Proteome of Antibody-Mediated Rejection: From Glomerulitis to Transplant Glomerulopathy
Author
Chauveau, Bertrand 1   VIAFID ORCID Logo  ; Anne-Aurélie Raymond 2   VIAFID ORCID Logo  ; Sylvaine Di Tommaso 3   VIAFID ORCID Logo  ; Visentin, Jonathan 4 ; Vermorel, Agathe 5 ; Dugot-Senant, Nathalie 6 ; Dourthe, Cyril 2 ; Jean-William Dupuy 7   VIAFID ORCID Logo  ; Déchanet-Merville, Julie 8 ; Jean-Paul Duong Van Huyen 9 ; Rabant, Marion 10 ; Couzi, Lionel 11 ; Saltel, Frédéric 2 ; Merville, Pierre 11   VIAFID ORCID Logo 

 CHU de Bordeaux, Service de Pathologie, Hôpital Pellegrin, Place Amélie Raba Léon, F-33000 Bordeaux, France; ImmunoConcEpT, CNRS, Université Bordeaux, UMR 5164, 146 Rue Léo Saignat, F-33000 Bordeaux, France; [email protected] (J.V.); [email protected] (J.D.-M.); [email protected] (L.C.); [email protected] (P.M.) 
 Plateforme Oncoprot, TBM-Core US 005, Université Bordeaux, F-33000 Bordeaux, France; [email protected] (A.-A.R.); [email protected] (S.D.T.); [email protected] (C.D.); [email protected] (F.S.); INSERM UMR1312, BoRdeaux Institute of onCology (BRIC), Université Bordeaux, F-33000 Bordeaux, France 
 Plateforme Oncoprot, TBM-Core US 005, Université Bordeaux, F-33000 Bordeaux, France; [email protected] (A.-A.R.); [email protected] (S.D.T.); [email protected] (C.D.); [email protected] (F.S.) 
 ImmunoConcEpT, CNRS, Université Bordeaux, UMR 5164, 146 Rue Léo Saignat, F-33000 Bordeaux, France; [email protected] (J.V.); [email protected] (J.D.-M.); [email protected] (L.C.); [email protected] (P.M.); Laboratoire d’Immunologie et Immunogénétique, CHU de Bordeaux, Hôpital Pellegrin, Place Amélie Raba Léon, F-33000 Bordeaux, France 
 CHU de Bordeaux, Service de Néphrologie, Transplantation Dialyse, Aphérèses, Hôpital Pellegrin, Place Amélie Raba Léon, F-33000 Bordeaux, France; [email protected] 
 Plateforme d’Histopathologie, TBM-Core US 005, Université Bordeaux, F-33000 Bordeaux, France; [email protected] 
 Plateforme Protéome, Université Bordeaux, F-33000 Bordeaux, France; [email protected] 
 ImmunoConcEpT, CNRS, Université Bordeaux, UMR 5164, 146 Rue Léo Saignat, F-33000 Bordeaux, France; [email protected] (J.V.); [email protected] (J.D.-M.); [email protected] (L.C.); [email protected] (P.M.) 
 Assistance Publique—Hôpitaux de Paris (AP-HP), Service de Pathologie, Hôpital Necker, F-75015 Paris, France; [email protected] (J.-P.D.V.H.); [email protected] (M.R.) 
10  Assistance Publique—Hôpitaux de Paris (AP-HP), Service de Pathologie, Hôpital Necker, F-75015 Paris, France; [email protected] (J.-P.D.V.H.); [email protected] (M.R.); INSERM U1151, F-75730 Paris, France 
11  ImmunoConcEpT, CNRS, Université Bordeaux, UMR 5164, 146 Rue Léo Saignat, F-33000 Bordeaux, France; [email protected] (J.V.); [email protected] (J.D.-M.); [email protected] (L.C.); [email protected] (P.M.); CHU de Bordeaux, Service de Néphrologie, Transplantation Dialyse, Aphérèses, Hôpital Pellegrin, Place Amélie Raba Léon, F-33000 Bordeaux, France; [email protected] 
First page
569
Publication year
2022
Publication date
2022
Publisher
MDPI AG
e-ISSN
22279059
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2642347396
Copyright
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.