TY - JOUR
T1 - Murine Cytomegalovirus-induced Complement-fixing Antibodies Deposit in Murine Renal Allografts during Acute Rejection
AU - Saunders, Ute
AU - Li, Mao
AU - Boddeda, Srinivasa R.
AU - Maher, Sonya
AU - Ghere, Jessica
AU - Kaptsan, Irina
AU - Dhital, Ravi
AU - Velazquez, Victoria
AU - Guo, Lingling
AU - Chen, Bo
AU - Zeng, Qiang
AU - Schoeb, Trenton R.
AU - Cianciolo, Rachel
AU - Shimamura, Masako
N1 - Publisher Copyright:
© 2021 Lippincott Williams and Wilkins. All rights reserved.
PY - 2021/8/1
Y1 - 2021/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85111309484&partnerID=8YFLogxK
U2 - 10.1097/TP.0000000000003548
DO - 10.1097/TP.0000000000003548
M3 - Article
C2 - 33214535
AN - SCOPUS:85111309484
SN - 0041-1337
VL - 105
SP - 1718
EP - 1729
JO - Transplantation
JF - Transplantation
IS - 8
ER -