Ute Saunders1, Mao Li1, Srinivasa R Boddeda2, Sonya Maher2, Jessica Ghere2, Irina Kaptsan2, Ravi Dhital2, Victoria Velazquez2, Lingling Guo3, Bo Chen3, Qiang Zeng4, Trenton R Schoeb5, Rachel Cianciolo6, Masako Shimamura2,7. 1. Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL. 2. Center for Vaccines and Immunity, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH. 3. Division of Cardiothoracic Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL. 4. Center for Regenerative Medicine, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH. 5. Department of Genetics, University of Alabama at Birmingham, Birmingham, AL. 6. Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH. 7. Division of Pediatric Infectious Diseases, Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH.
Abstract
BACKGROUND: Human cytomegalovirus (CMV) infection is associated with renal allograft dysfunction and loss, particularly in combination with acute rejection. Emerging literature suggests that non-HLA antibodies may contribute to antibody-mediated rejection, but pathogen-induced antibodies have not been investigated in this context. This study examines the presence of CMV-induced antibodies in murine CMV (MCMV)-infected renal allografts during acute rejection. METHODS: Intragraft immunoglobulin G (IgG) and complement C3 immunostaining were compared among allogeneic MCMV D-/R-, D+/R-, and D+/R+ renal transplants. Intragraft antibody deposition was examined in B cell-deficient recipients treated with MCMV immune sera. Antibody binding and complement-dependent cytotoxicity (CDC) of D-/R- and D+/R+ sera against infected renal tubular epithelial cells (TECs) were measured in vitro. IgG immunostaining was performed in D+/R+ allografts and native kidneys and in D+/R- allografts treated with ganciclovir to inhibit viral replication. RESULTS: D+/R- and D+/R+ transplants had more abundant IgG and C3 deposition compared with D-/R- recipients. Greater IgG deposition was associated with more severe allograft injury in B cell-deficient recipients treated with MCMV immune sera compared with nonimmune sera. D+/R+ sera induced greater CDC of infected TECs compared with D-/R- sera. Native kidneys had lower IgG deposition compared with allografts, despite similar organ viral loads. Ganciclovir-treated allografts had reduced IgG deposition compared with untreated allografts. CONCLUSIONS: In this murine model, complement-fixing antibodies can deposit into MCMV-infected renal allografts, are associated with allograft damage, and can induce CDC of MCMV-infected renal TECs. The allogeneic response and viral replication may also contribute to intragraft antibody deposition.
BACKGROUND: Human cytomegalovirus (CMV) infection is associated with renal allograft dysfunction and loss, particularly in combination with acute rejection. Emerging literature suggests that non-HLA antibodies may contribute to antibody-mediated rejection, but pathogen-induced antibodies have not been investigated in this context. This study examines the presence of CMV-induced antibodies in murine CMV (MCMV)-infected renal allografts during acute rejection. METHODS: Intragraft immunoglobulin G (IgG) and complement C3 immunostaining were compared among allogeneic MCMV D-/R-, D+/R-, and D+/R+ renal transplants. Intragraft antibody deposition was examined in B cell-deficient recipients treated with MCMV immune sera. Antibody binding and complement-dependent cytotoxicity (CDC) of D-/R- and D+/R+ sera against infected renal tubular epithelial cells (TECs) were measured in vitro. IgG immunostaining was performed in D+/R+ allografts and native kidneys and in D+/R- allografts treated with ganciclovir to inhibit viral replication. RESULTS: D+/R- and D+/R+ transplants had more abundant IgG and C3 deposition compared with D-/R- recipients. Greater IgG deposition was associated with more severe allograft injury in B cell-deficient recipients treated with MCMV immune sera compared with nonimmune sera. D+/R+ sera induced greater CDC of infected TECs compared with D-/R- sera. Native kidneys had lower IgG deposition compared with allografts, despite similar organ viral loads. Ganciclovir-treated allografts had reduced IgG deposition compared with untreated allografts. CONCLUSIONS: In this murine model, complement-fixing antibodies can deposit into MCMV-infected renal allografts, are associated with allograft damage, and can induce CDC of MCMV-infected renal TECs. The allogeneic response and viral replication may also contribute to intragraft antibody deposition.
Authors: M Haas; A Loupy; C Lefaucheur; C Roufosse; D Glotz; D Seron; B J Nankivell; P F Halloran; R B Colvin; Enver Akalin; N Alachkar; S Bagnasco; Y Bouatou; J U Becker; L D Cornell; J P Duong van Huyen; I W Gibson; Edward S Kraus; R B Mannon; M Naesens; V Nickeleit; P Nickerson; D L Segev; H K Singh; M Stegall; P Randhawa; L Racusen; K Solez; M Mengel Journal: Am J Transplant Date: 2018-01-21 Impact factor: 8.086
Authors: María Iglesias-Escudero; Marco Antonio Moro-García; Raquel Marcos-Fernández; Alejandra García-Torre; Marta Elena Álvarez-Argüelles; María Luisa Suárez-Fernández; Pablo Martínez-Camblor; Minerva Rodríguez; Rebeca Alonso-Arias Journal: PLoS One Date: 2018-04-11 Impact factor: 3.240
Authors: Tomas Reischig; Martin Kacer; Petra Hruba; Hana Hermanova; Ondrej Hes; Daniel Lysak; Stanislav Kormunda; Mirko Bouda Journal: BMC Infect Dis Date: 2018-11-15 Impact factor: 3.090
Authors: Ravi Dhital; Shashi Anand; Brianna Graber; Qiang Zeng; Victoria M Velazquez; Srinivasa R Boddeda; James R Fitch; Ranjana W Minz; Mukut Minz; Ashish Sharma; Rachel Cianciolo; Masako Shimamura Journal: Am J Transplant Date: 2022-06-15 Impact factor: 9.369