Title :

Early Acute Microvascular Kidney Transplant Rejection in the Absence of Anti-HLA Antibodies Is Associated with Preformed IgG Antibodies against Diverse Glomerular Endothelial Cell Antigens.

Author(s) :

Delville, Marianne [Auteur]
Imagine - Institut des maladies génétiques (IHU) [Imagine - U1163]
Lamarthee, Baptiste [Auteur]
Institut Necker Enfants-Malades [INEM - UM 111 (UMR 8253 / U1151)]
Pagie, Sylvain [Auteur]
Centre de Recherche en Transplantation et Immunologie [U1064 Inserm - CRTI]
See, Sarah B [Auteur]
Rabant, Marion [Auteur]
Université Paris Cité [UPCité]
Burger, Carole [Auteur]
Université Paris Descartes - Paris 5 [UPD5]
Gatault, Philippe [Auteur]
Université de Tours [UT]
Giral, Magali [Auteur]
Institut de Transplantation et de Recherche en Transplantation [CHU Nantes] [ITERT]
Thaunat, Olivier [Auteur]
Université Claude Bernard Lyon 1 [UCBL]
Arzouk, Nadia [Auteur]
CHU Pitié-Salpêtrière [AP-HP]
Hertig, Alexandre [Auteur]
Sorbonne Université [SU]
Hazzan, Marc [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Matignon, Marie [Auteur]
Université Paris-Est Créteil Val-de-Marne - Paris 12 [UPEC UP12]
Mariat, Christophe [Auteur]
Université Jean Monnet - Saint-Étienne [UJM]
Caillard, Sophie [Auteur]
Centre Hospitalier Universitaire [Strasbourg] [CHU Strasbourg]
Kamar, Nassim [Auteur]
Université Toulouse III - Paul Sabatier [UT3]
Sayegh, Johnny [Auteur]
Université d'Angers [UA]
Westeel, Pierre-Francois [Auteur]
CHU Amiens-Picardie
Garrouste, Cyril [Auteur]
CHU Clermont-Ferrand
Ladriere, Marc [Auteur]
Service de Cardiologie et Transplantation [CHRU Nancy]
Vuiblet, Vincent [Auteur]
Hôpital universitaire Robert Debré [Reims] [CHU Reims]
Rivalan, Joseph [Auteur]
Service de néphrologie [Rennes]
Merville, Pierre [Auteur]
Université de Bordeaux [UB]
Bertrand, Dominique [Auteur]
CHU Rouen
Le Moine, Alain [Auteur]
Université libre de Bruxelles [ULB]
Duong Van Huyen, Jean Paul [Auteur]
Université Paris Descartes - Paris 5 [UPD5]
Cesbron, Anne [Auteur]
Etablissement Français du Sang [Nantes]
Cagnard, Nicolas [Auteur]
Structure Fédérative de Recherche Necker [UAR 3633 / US24]
Alibeu, Olivier [Auteur]
Structure Fédérative de Recherche Necker [UAR 3633 / US24]
Satchell, Simon C. [Auteur]
University of Bristol [Bristol]
Legendre, Christophe M. [Auteur]
Hôpital Necker - Enfants Malades [AP-HP]
Zorn, Emmanuel [Auteur]
Taupin, Jean-Luc [Auteur]
Université Paris Diderot - Paris 7 [UPD7]
Charreau, Beatrice [Auteur]
Nantes Université [Nantes Univ]
Anglicheau, Dany [Auteur]
Hôpital Necker - Enfants Malades [AP-HP]

Journal title :

Journal of the American Society of Nephrology

Abbreviated title :

J. Am. Soc. Nephrol.

Volume number :

30

Pages :

692-709

Publication date :

2019-04

ISSN :

1533-3450

English keyword(s) :

acute rejection
acute microvascular rejection
AECAs
antibody mediated rejection

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

BACKGROUND: Although anti-HLA antibodies (Abs) cause most antibody-mediated rejections of renal allografts, non-anti-HLA Abs have also been postulated to contribute. A better understanding of such Abs in rejection is ...
Show more >BACKGROUND: Although anti-HLA antibodies (Abs) cause most antibody-mediated rejections of renal allografts, non-anti-HLA Abs have also been postulated to contribute. A better understanding of such Abs in rejection is needed. METHODS: We conducted a nationwide study to identify kidney transplant recipients without anti-HLA donor-specific Abs who experienced acute graft dysfunction within 3 months after transplantation and showed evidence of microvascular injury, called acute microvascular rejection (AMVR). We developed a crossmatch assay to assess serum reactivity to human microvascular endothelial cells, and used a combination of transcriptomic and proteomic approaches to identify non-HLA Abs. RESULTS: We identified a highly selected cohort of 38 patients with early acute AMVR. Biopsy specimens revealed intense microvascular inflammation and the presence of vasculitis (in 60.5%), interstitial hemorrhages (31.6%), or thrombotic microangiopathy (15.8%). Serum samples collected at the time of transplant showed that previously proposed anti-endothelial cell Abs-angiotensin type 1 receptor (AT1R), endothelin-1 type A and natural polyreactive Abs-did not increase significantly among patients with AMVR compared with a control group of stable kidney transplant recipients. However, 26% of the tested AMVR samples were positive for AT1R Abs when a threshold of 10 IU/ml was used. The crossmatch assay identified a common IgG response that was specifically directed against constitutively expressed antigens of microvascular glomerular cells in patients with AMVR. Transcriptomic and proteomic analyses identified new targets of non-HLA Abs, with little redundancy among individuals. CONCLUSIONS: Our findings indicate that preformed IgG Abs targeting non-HLA antigens expressed on glomerular endothelial cells are associated with early AMVR, and that cell-based assays are needed to improve risk assessments before transplant.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CHU Lille
Inserm
Université de Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Submission date :

2019-10-22T08:17:04Z
2024-03-27T09:51:03Z