Alexander Fichtner1, Caner Süsal2, Claudia Schröder1, Britta Höcker1, Susanne Rieger1, Rüdiger Waldherr3, Jens H Westhoff1, Anja Sander4, Duska Dragun5,6, Burkhard Tönshoff1. 1. Department of Paediatrics I, University Children's Hospital, Heidelberg, Germany. 2. Department of Transplantation Immunology, Institute of Immunology, University of Heidelberg, Heidelberg, Germany. 3. Department of Nephropathology, Institute of Clinical Pathology, Heidelberg, Germany. 4. Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany. 5. Clinic for Nephrology and Critical Care Medicine, Charite-Universitatsmedizin Berlin, corporate member of Freie Universitat Berlin, Humboldt-Universitat zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany. 6. Berlin Institute of Health, Berlin, Germany.
Abstract
Background: We analysed in a carefully phenotyped cohort of paediatric patients the association of serum angiotensin II type 1 receptor antibodies (AT1R-Ab) with specific histological lesions and with graft function and survival in conjunction with overall and complement-binding donor-specific human leucocyte antigen donor-specific antibodies (HLA-DSA). Methods: Sera of 62 patients at the time of renal graft biopsy for clinical indication >1 year post-transplant were assessed for AT1R-Ab by enzyme-linked immunosorbent assay (ELISA) and for DSA and C1q-fixing DSA by single-antigen bead technology. Results: Serum AT1R-Ab concentration was significantly higher in antibody-mediated rejection (ABMR) than in T-cell-mediated rejection or control. By receiver operating characteristic (ROC) curve analysis, the optimal AT1R-Ab cut-off value discriminating between patients with features of ABMR and those without was 9.5 U/mL. A total of 6 of 28 patients (21.4%) with ABMR were only positive for AT1R-Ab. Patients with AT1R-Ab and HLA-DSA double positivity had a significantly higher vascular micro-inflammation score than DSA-negative patients. The 5-year graft survival was only 59% in the AT1R-Ab-positive group compared with 87% in the AT1R-Ab-negative group. Patients with AT1R-Ab and HLA-DSA double positivity tended to have a more rapid decline of estimated glomerular filtration rate (eGFR) than patients who were only positive for AT1R-Ab or HLA-DSA. In a multivariate Cox regression model of non-invasive factors, C1q-positive HLA-DSA, eGFR and AT1R-Ab positivity were significantly associated with accelerated graft function decline. Conclusions: Serum AT1R-Ab positivity in the context of an indication biopsy >1 year post-transplant is associated with the histopathology of ABMR and is an independent non-invasive risk factor for adverse graft outcome.
Background: We analysed in a carefully phenotyped cohort of paediatric patients the association of serum angiotensin II type 1 receptor antibodies (AT1R-Ab) with specific histological lesions and with graft function and survival in conjunction with overall and complement-binding donor-specific human leucocyte antigen donor-specific antibodies (HLA-DSA). Methods: Sera of 62 patients at the time of renal graft biopsy for clinical indication >1 year post-transplant were assessed for AT1R-Ab by enzyme-linked immunosorbent assay (ELISA) and for DSA and C1q-fixing DSA by single-antigen bead technology. Results: Serum AT1R-Ab concentration was significantly higher in antibody-mediated rejection (ABMR) than in T-cell-mediated rejection or control. By receiver operating characteristic (ROC) curve analysis, the optimal AT1R-Ab cut-off value discriminating between patients with features of ABMR and those without was 9.5 U/mL. A total of 6 of 28 patients (21.4%) with ABMR were only positive for AT1R-Ab. Patients with AT1R-Ab and HLA-DSA double positivity had a significantly higher vascular micro-inflammation score than DSA-negative patients. The 5-year graft survival was only 59% in the AT1R-Ab-positive group compared with 87% in the AT1R-Ab-negative group. Patients with AT1R-Ab and HLA-DSA double positivity tended to have a more rapid decline of estimated glomerular filtration rate (eGFR) than patients who were only positive for AT1R-Ab or HLA-DSA. In a multivariate Cox regression model of non-invasive factors, C1q-positive HLA-DSA, eGFR and AT1R-Ab positivity were significantly associated with accelerated graft function decline. Conclusions: Serum AT1R-Ab positivity in the context of an indication biopsy >1 year post-transplant is associated with the histopathology of ABMR and is an independent non-invasive risk factor for adverse graft outcome.
Authors: Meghan H Pearl; Lucia Chen; Rim ElChaki; David Elashoff; David W Gjertson; Maura Rossetti; Patricia L Weng; Qiuheng Zhang; Elaine F Reed; Eileen Tsai Chambers Journal: Kidney Int Rep Date: 2020-09-06
Authors: Meghan H Pearl; Jonathan Grotts; Maura Rossetti; Qiuheng Zhang; David W Gjertson; Patricia Weng; David Elashoff; Elaine F Reed; Eileen Tsai Chambers Journal: Kidney Int Rep Date: 2018-12-21
Authors: Marianne Delville; Baptiste Lamarthée; Sylvain Pagie; Sarah B See; Marion Rabant; Carole Burger; Philippe Gatault; Magali Giral; Olivier Thaunat; Nadia Arzouk; Alexandre Hertig; Marc Hazzan; Marie Matignon; Christophe Mariat; Sophie Caillard; Nassim Kamar; Johnny Sayegh; Pierre-François Westeel; Cyril Garrouste; Marc Ladrière; Vincent Vuiblet; Joseph Rivalan; Pierre Merville; Dominique Bertrand; Alain Le Moine; Jean-Paul Duong Van Huyen; Anne Cesbron; Nicolas Cagnard; Olivier Alibeu; Simon C Satchell; Christophe Legendre; Emmanuel Zorn; Jean-Luc Taupin; Béatrice Charreau; Dany Anglicheau Journal: J Am Soc Nephrol Date: 2019-03-08 Impact factor: 10.121