Purpose: Cytomegalovirus (CMV) infection morbidity and prophylactic CMV antiviral toxicities remain significant in pediatric solid organ transplantation (PSOT). The utility of CMV T cell immunity (TCI) assays in stratifying post-transplant CMV infection risk has not been well studied in PSOT.
Methods: We conducted a prospective multicenter study of the flow cytometry-based CMV inSIGHT^TM T Cell Immunity (TCI) Assay (Eurofins-Viracor). This assay quantifies whole blood CD4+ and CD8+T cell IFNγ expression following CMV antigen mixture or pp65 peptide stimulation. A threshold of >0.20% IFNγ+ cells is defined as a positive response. PSOT recipients (<18 years) who were donorand/or recipient CMV seropositive were enrolled pre-transplant and followed for 12 months post-SOT. We tested the hypothesis that CMV TCI assay positivity measured at 3- and 6- months post-transplant is associated with decreased frequency of subsequent first-episode CMV DNAemia. Statistical analysis was performed using Firth’s penalized logistic regression.
Results: Seventy-seven evaluable participants contributed to this analysis (Figure 1). Twenty-two episodes of first CMV infection were identified (28.6% of participants). Amongst these first-episode infections were 16 asymptomatic CMV DNAemia episodes, five CMV viral syndrome episodes, and one occurrence of CMV disease. Using positivity cutoffs previously defined in adult patients, positive CD4+ or CD8+ CMV TCI at 3 months or 6months post-transplant was not associated with decreased risk of subsequent CMV DNAemia (Figure 2). This lack of association held when adjusting for duration of CMV prophylaxis or for CMVserostatus and when limiting CMV DNAemia event occurrence to 90 days following CMV TCI sample measurement. No significant differences in frequency of IFNγ+ CD4+ or CD8+ T cells were notedwhen compared between participants with or without a first post-transplant episode of CMV DNAemia after the 3- or 6-month CMV TCI timepoints (Figure 2).
Conclusions: CMV TCI measured at 3- and 6-months post-transplantation in PSOT is not associated with decreased risk of subsequent first episode CMV infection within the first-year post-transplantation. Study limitations, including between-site variation in CMV DNAemia screening frequency, may have precluded detecting a significant association. Future analyses will evaluate alternative CMV TCI positivity cutoffs and assess the association between CMV TCI and symptomatic CMV infection (viral syndrome and/or tissue invasive disease)