Jonathan-Maurice Chemouny1, Caroline Suberbielle, Marion Rabant, Julien Zuber, Marie-Alexandra Alyanakian, Xavier Lebreton, Maryvonnick Carmagnat, Nathan Pinheiro, Alexandre Loupy, Jean-Paul Van Huyen, Marc-Olivier Timsit, Dominique Charron, Christophe Legendre, Dany Anglicheau. 1. 1 INSERM U1149, Paris, France. 2 Université Paris 7-Denis Diderot, Paris, France. 3 Laboratoire Régional d'Histocompatibilité, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France. 4 Laboratoire D'Anatomie Pathologique, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, Paris, France. 5 Service de Néphrologie et Transplantation Adulte, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, Paris, France. 6 Université Paris Descartes, Sorbonne Paris Cité, Paris, France. 7 RTRS Centaure, Labex Transplantex, Paris, France. 8 Laboratoire D'Immunologie, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, Paris, France. 9 Service D'Urologie, HEGP-Necker, Assistance Publique-Hôpitaux de Paris, Paris, France. 10 INSERM U1151, Paris, France.
Abstract
BACKGROUND: Local inflammation is a potential cause of humoral alloimmune responses in renal transplantation, and de novo donor-specific anti-human leucocyte antigen antibodies (dnDSAs) have been associated with a history of acute rejection. METHODS: We investigated the frequencies and consequences of dnDSAs after a first episode of acute T-cell-mediated rejection (index TCMR) in previously unsensitized kidney transplant recipients. RESULTS: Of the 1,054 patients who underwent kidney transplantation between September 2004 and December 2010 at our center, we identified 75 unsensitized patients with at least one TCMR. Index TCMRs were diagnosed 4.4 ± 6.8 months after transplantation. The dnDSAs were assessed using the highly sensitive single-antigen human leukocyte antigen bead assay 5.1 ± 3.9 months after the index TCMR and were detected in 16 patients (21%). Patients who developed dnDSAs were more likely to have experienced pre-transplant sensitizing events and were indistinguishable in their clinical, biologic, and histologic variables at the time of index TCMR, although the tubulitis scores tended to be higher (P = 0.079). These patients experienced a significantly higher incidence of subsequent antibody-mediated rejection episodes (P < 0.001), but reduced death-censored graft survival was not observed after a median follow-up of 5.5 years post-transplantation. Follow-up biopsies revealed increased antibody-mediated changes with significantly higher glomerulitis scores and numerically higher C4d staining scores. CONCLUSION: Monitoring anti-human leukocyte antigen antibodies after cellular rejection may be useful, especially among patients with a history of pretransplant exposure to alloantigens, to predict subsequent humoral events and their consequences.
BACKGROUND: Local inflammation is a potential cause of humoral alloimmune responses in renal transplantation, and de novo donor-specific anti-human leucocyte antigen antibodies (dnDSAs) have been associated with a history of acute rejection. METHODS: We investigated the frequencies and consequences of dnDSAs after a first episode of acute T-cell-mediated rejection (index TCMR) in previously unsensitized kidney transplant recipients. RESULTS: Of the 1,054 patients who underwent kidney transplantation between September 2004 and December 2010 at our center, we identified 75 unsensitized patients with at least one TCMR. Index TCMRs were diagnosed 4.4 ± 6.8 months after transplantation. The dnDSAs were assessed using the highly sensitive single-antigen human leukocyte antigen bead assay 5.1 ± 3.9 months after the index TCMR and were detected in 16 patients (21%). Patients who developed dnDSAs were more likely to have experienced pre-transplant sensitizing events and were indistinguishable in their clinical, biologic, and histologic variables at the time of index TCMR, although the tubulitis scores tended to be higher (P = 0.079). These patients experienced a significantly higher incidence of subsequent antibody-mediated rejection episodes (P < 0.001), but reduced death-censored graft survival was not observed after a median follow-up of 5.5 years post-transplantation. Follow-up biopsies revealed increased antibody-mediated changes with significantly higher glomerulitis scores and numerically higher C4d staining scores. CONCLUSION: Monitoring anti-human leukocyte antigen antibodies after cellular rejection may be useful, especially among patients with a history of pretransplant exposure to alloantigens, to predict subsequent humoral events and their consequences.
Authors: Elena Crespo; Paolo Cravedi; Jaume Martorell; Sergi Luque; Edoardo Melilli; Josep M Cruzado; Marta Jarque; Maria Meneghini; Anna Manonelles; Chiara Donadei; Núria Lloberas; Montse Gomà; Josep M Grinyó; Peter Heeger; Oriol Bestard Journal: Kidney Int Date: 2017-03-06 Impact factor: 10.612
Authors: A I Dipchand; S Webber; K Mason; B Feingold; C Bentlejewski; W T Mahle; R Shaddy; C Canter; E D Blume; J Lamour; W Zuckerman; H Diop; Y Morrison; B Armstrong; D Ikle; J Odim; A Zeevi Journal: Am J Transplant Date: 2018-03-24 Impact factor: 8.086
Authors: Chris Wiebe; David N Rush; Ian W Gibson; Denise Pochinco; Patricia E Birk; Aviva Goldberg; Tom Blydt-Hansen; Martin Karpinski; Jamie Shaw; Julie Ho; Peter W Nickerson Journal: Am J Transplant Date: 2020-04-09 Impact factor: 8.086