Sara van den Berg

187 7 Duration of CMV infection Figure 4. CMV-induced changes in the CD4+ T-cell pool are established early after CMV infection, and are most pronounced in older CMV-seroconverters. A. Absolute numbers of CD4+ T-cell subsets compared between CMV-, ST CMV+, and LT CMV+ individuals indicated by geometric mean with geometric standard deviation. B. Relationship of duration of CMV infection with CD4+ T EMRA cells numbers. ρ and p value are from correlation tested in ST CMV+ individuals. C. CD4+ T EMRA cells numbers at endpoint are compared between individuals that seroconverted at younger age (≤38yr) or older age (seroconverted ≥45yr, mean age 58.5±8.1). D,E. Correlation of CD4 T EMRA cells numbers with their percentage producing granzyme B and perforin ( D ) and IFN γ production after CMV-peptide stimulation (n=27) ( E ). F. Percentages of CD4 T-cells producing IFN γ after CMV-specific stimulation in CMV-, ST CMV+, and LT CMV+ individuals. H. Percentage of CD4+ T-cells respond- ing polyfunctionally to CMV with production of IFN γ , TNFa, MIP-1 β , and/or CD107 in ST CMV+ and LT CMV+ individuals. *=P<0.05, **=P<0.01, ***=P<0.001, ****=P<0.0001. Colors of symbols represent CMV-serostatus. Green: CMV-, blue: ST CMV+, purple: LT CMV+. Interestingly, within the group of ST CMV+ individuals, older age at CMV seroconversion was associated with a higher frailty index (p=0.03, ρ = 0.48) ( Figure 5C ), which reduced to a non-significant trend after adjusting for age at frailty index assessment (p=0.11, ρ =0.39). We further studied whether CMV-specific antibody levels at endpoint or the increase of CMV-specific antibodies per year were associated with frailty. None of these two indicators were significantly associated with frailty ( Figure 5D,E ). The median increase in frailty

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