Dissection of the HCMV-Specific Antibody Responses in Lung-Transplant Recipients

Purpose Human Cytomegalovirus (HCMV) is an important viral pathogen in lung-transplant recipients (LTRs), which may cause generalized infection and tissue-invasive disease. The risk for HCMV-replication depends on the donor (D) and recipient (R) serostatus as well as on HCMV-specific immune responses such as HCMV-specific antibodies (AB) and NK-cells, which may limit viral spread after lung-transplantation. In this study we analyzed the glycoprotein B (gB) and pentameric complex (PC)-specific AB-responses as well as the antibodies’ neutralizing and NK-cell activating effector functions following lung transplantation. Methods 35 R+, 26 D+/R- LTRs, who received a lung transplant between 2013 and 2016 at the Medical University of Vienna and 134 non-transplanted control individuals were included in the study. From each transplanted patient, follow-up plasma samples were collected in a three-month interval in a one (R+) or two (D+/R-) year period post-transplantation. PC-specific as well as gB-specific IgG titers were determined by ELISA. 50% neutralizing titers were determined with epithelial cells, fibroblasts and the laboratory strain TB40E-BAC4. The NK-cell response was determined using NK92-CD16a cells in a serum-dependent focal expansion and a CD107 cytotoxicity assay. Results The R+ LTRs reached a higher level of gB- but not of PC-specific IgG-titers in the first year post-transplantation compared to healthy seropositive individuals (IgG1 one year post-transplantation gB: p Conclusion From the present data it appears that R+ patients with pre-existing HCMV-specific ABs show a high level of NK-cell activation by gB-specific ABs.