Jamal Bamoulid1, Afaf Roodenburg, Oliver Staeck, Kaiyin Wu, Birgit Rudolph, Susanne Brakemeier, Fabian Halleck, Lukas Lehner, Constanze Schönemann, Nils Lachmann, Klemens Budde. 1. 1 Department of Nephrology, Campus Charité Mitte, Charité Universitätsmedizin, Berlin, Germany. 2 HLA Laboratory, Campus Virchow Klinikum, Charité Universitätsmedizin, Berlin, Germany. 3 INSERM, UMR1098, Federation Hospitalo-Universitaire INCREASE, Besançon, France. 4 Université de Franche-Comté, Faculté de Médecine et de Pharmacie, Besançon, France. 5 Department of Hospital Pharmacy, Erasmus University Medical Centre, Rotterdam, The Netherlands. 6 Department of Pathology, Campus Charite Mitte, Charité Universitätsmedizin, Berlin, Germany.
Abstract
BACKGROUND: De novo donor specific anti-HLA antibodies (dnDSA) may cause graft loss in renal transplant recipients. The capability to bind the complement may help to stratify the risk for inferior outcomes associated with dnDSA. We developed a modified C1q-binding assay and hypothesized that C1q-binding dnDSA could differentiate between indolent and harmful dnDSA causing antibody-mediated rejection (AMR) and graft loss. METHODS: We retrospectively identified 59 renal transplant recipients who developed dnDSA and had serum available and complete follow-up. All patients were analyzed for C1q-binding dnDSA at the time of dnDSA detection, and 1-year later or at time of AMR. AMR-positive patients were also tested 6 to 12 months before the event if IgG dnDSA was present. RESULTS: Thirty-seven of 59 dnDSA patients developed AMR during 5.9 ± 3.1 years follow-up. AMR-positive patients had more dnDSA with a significant higher frequency of class I, a higher frequency and a higher mean fluorescence intensity value of C1q-dnDSA at all time-points. Death-censored AMR-free and allograft survivals were significantly lower in C1q-dnDSA patients. In multivariate analysis, C1q-dnDSA was an independent risk factor for AMR. CONCLUSIONS: C1q-binding dnDSA is associated with inferior outcomes, yet not in all patients. Nevertheless, C1q-dnDSA was shown to be an independent risk factor of AMR and graft loss and may be a useful tool to stratify the immunological risk for AMR.
BACKGROUND: De novo donor specific anti-HLA antibodies (dnDSA) may cause graft loss in renal transplant recipients. The capability to bind the complement may help to stratify the risk for inferior outcomes associated with dnDSA. We developed a modified C1q-binding assay and hypothesized that C1q-binding dnDSA could differentiate between indolent and harmful dnDSA causing antibody-mediated rejection (AMR) and graft loss. METHODS: We retrospectively identified 59 renal transplant recipients who developed dnDSA and had serum available and complete follow-up. All patients were analyzed for C1q-binding dnDSA at the time of dnDSA detection, and 1-year later or at time of AMR. AMR-positive patients were also tested 6 to 12 months before the event if IgG dnDSA was present. RESULTS: Thirty-seven of 59 dnDSApatients developed AMR during 5.9 ± 3.1 years follow-up. AMR-positive patients had more dnDSA with a significant higher frequency of class I, a higher frequency and a higher mean fluorescence intensity value of C1q-dnDSA at all time-points. Death-censored AMR-free and allograft survivals were significantly lower in C1q-dnDSApatients. In multivariate analysis, C1q-dnDSA was an independent risk factor for AMR. CONCLUSIONS:C1q-binding dnDSA is associated with inferior outcomes, yet not in all patients. Nevertheless, C1q-dnDSA was shown to be an independent risk factor of AMR and graft loss and may be a useful tool to stratify the immunological risk for AMR.
Authors: A Loupy; M Haas; K Solez; L Racusen; D Glotz; D Seron; B J Nankivell; R B Colvin; M Afrouzian; E Akalin; N Alachkar; S Bagnasco; J U Becker; L Cornell; C Drachenberg; D Dragun; H de Kort; I W Gibson; E S Kraus; C Lefaucheur; C Legendre; H Liapis; T Muthukumar; V Nickeleit; B Orandi; W Park; M Rabant; P Randhawa; E F Reed; C Roufosse; S V Seshan; B Sis; H K Singh; C Schinstock; A Tambur; A Zeevi; M Mengel Journal: Am J Transplant Date: 2017-01 Impact factor: 8.086
Authors: Antoine Bouquegneau; Charlotte Loheac; Olivier Aubert; Yassine Bouatou; Denis Viglietti; Jean-Philippe Empana; Camilo Ulloa; Mohammad Hassan Murad; Christophe Legendre; Denis Glotz; Annette M Jackson; Adriana Zeevi; Stephan Schaub; Jean-Luc Taupin; Elaine F Reed; John J Friedewald; Dolly B Tyan; Caner Süsal; Ron Shapiro; E Steve Woodle; Luis G Hidalgo; Jacqueline O'Leary; Robert A Montgomery; Jon Kobashigawa; Xavier Jouven; Patricia Jabre; Carmen Lefaucheur; Alexandre Loupy Journal: PLoS Med Date: 2018-05-25 Impact factor: 11.069
Authors: Clara Fischman; Miguel Fribourg; Ginevri Fabrizio; Michela Cioni; Patrizia Comoli; Arcangelo Nocera; Massimo Cardillo; Chiara Cantarelli; Lorenzo Gallon; Astgik Petrosyan; Stefano Da Sacco; Laura Perin; Paolo Cravedi Journal: Transplant Direct Date: 2019-08-08