Functional signatures are associated with risk of clinically significant CMV. (A) The skewed distribution of the NPS (IL-2⁻IFN-γ⁺TNF-α-ΜIP-1β⁺ cells within the CMV(pp65)-specific CD8⁺ T-cell compartment) in patients with clinically significant CMV. (B) A trend toward reduced levels of the PS (IL-2⁺IFN-γ⁺TNF-α⁺MIP-1β⁺ cells) in patients with clinically significant CMV. (A-B) Immunophenotyping was performed on day +30. Medians with IQR are shown for each group. Differences between groups by using Mann-Whitney U test are shown. EC (n = 13); SC (n = 16); NC (n = 13). (C-E) Cumulative incidence of clinically significant CMV by levels of NPS using 16% as cutoff (C); by levels of PS using 0.45 as cutoff (D); and by a composite biomarker consisting of high levels of NPS and low levels of PS using above cutoffs (E). Specific cutoffs were identified using the most significant P value approach. Number of subjects in log-rank analysis shown in panel C was 19 and 17 for low and high NPS groups, respectively. Number of subjects in log-rank analysis shown in panel D was 10 and 26 for low and high PS groups, respectively. Number of subjects in log-rank analysis in panel E was 6 and 30 for composite biomarker and other signatures, respectively. Note increased cumulative incidence of clinically significant CMV infection in patients with high levels of the NPS, low levels of PS, and those with the composite biomarker.