Evaluating longitudinal cytomegalovirus-specific humoral immune responses and association with DNAemia risk in seropositive lung transplant recipients.

Cytomegalovirus (CMV) is the most common viral infection among lung transplant recipients and is associated with chronic lung allograft dysfunction. There is a need for better therapeutics as well as biomarkers to enable effective stratification of CMV seropositive patient risk for developing CMV DNAemia to inform prophylaxis duration. CMV-specific immunoglobulin G (IgG) binding and functional responses were evaluated in a discovery cohort of longitudinal plasma samples from 51 CMV seropositive human lung transplant recipients, collected as part of the clinical trials in organ transplantation (CTOT)-20 and CTOT-22 consortium studies. Pre-transplant plasma from an additional 43 CMV seropositive lung transplant recipients was evaluated as a validation cohort. In the discovery cohort with longitudinal samples, pre-transplant plasma IgG binding to CMV surface glycoproteins glycoprotein H (gH)/glycoprotein L (gL), gH/gL/glycoprotein O (gO), and pentameric complex, as well as neutralization of CMV in epithelial cells, is associated with increased risk of CMV DNAemia post-prophylaxis. However, these results were not confirmed by the validation cohort. While quantification of pre-transplant CMV-specific antibody responses showed association with DNAemia in the discovery cohort, additional clinical variables and/or known risk factors for CMV, such as patient CMV-specific T-cell responses, may need to be considered in combination with humoral immunity to effectively stratify risk of CMV DNAemia.