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

## TL;DR

This study examines how CMV-specific antibodies in lung transplant recipients relate to the risk of CMV DNAemia, but finds inconsistent results between two groups.

## Contribution

The study explores longitudinal CMV-specific humoral immune responses and their association with DNAemia risk in lung transplant recipients.

## Key findings

- Pre-transplant CMV-specific IgG binding to certain glycoproteins is linked to increased DNAemia risk in the discovery cohort.
- Results from the discovery cohort were not confirmed in the validation cohort.
- Combining humoral immunity with other factors may be needed to accurately assess CMV DNAemia risk.

## Abstract

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.