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.
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.
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.
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.