Abstract

BackgroundInfection with human cytomegalovirus (CMV) affects the function and composition of the immune system during ageing. In addition to the presence of the pathogen, the strength of the immune response, as measured by the anti-CMV IgG titre, has a significant effect on age-related pathogenesis. High anti-CMV IgG titres have been associated with increased mortality and functional impairment in the elderly. In this study, we were interested in identifying the molecular mechanisms that are associated with the strength of the anti-CMV response by examining the gene expression profiles that are associated with the level of the anti-CMV IgG titre.ResultsThe level of the anti-CMV IgG titre is associated with the expression level of 663 transcripts in nonagenarians. These transcripts and their corresponding pathways are, for the most part, associated with metabolic functions, cell development and proliferation and other basic cellular functions. However, no prominent associations with the immune system were found, and no associated transcripts were found in young controls.ConclusionsThe lack of defence pathways associated with the strength of the anti-CMV response can indicate that the compromised immune system can no longer defend itself against the CMV infection. Our data imply that the association between high anti-CMV IgG titres and increased mortality and frailty is mediated by basic cellular processes.

Highlights

  • Infection with human cytomegalovirus (CMV) affects the function and composition of the immune system during ageing

  • As in previous studies, a higher titre was associated with functional impairments in nonagenarians as the anti-CMV IgG titre was inversely correlated with handgrip strength (n = 130, Spearman’s rho = −0.233 p = 0.011) and the Barthel index (n = 138, Spearman’s rho = −0.218, p = 0.010)

  • To elucidate the molecular mechanisms that are associated with the strength of the anti-CMV immune response, as measured by the anti-CMV IgG titre, we performed a correlation analysis between the level of the antiCMV IgG titre and global gene expression levels

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Summary

Introduction

Infection with human cytomegalovirus (CMV) affects the function and composition of the immune system during ageing. In addition to the presence of the pathogen, the strength of the immune response, as measured by the anti-CMV IgG titre, has a significant effect on age-related pathogenesis. High anti-CMV IgG titres have been associated with increased mortality and functional impairment in the elderly. Several epidemiological studies imply that the strength of the anti-CMV response, quantitated based on the antiCMV titre, is of significance in age-related pathogenesis (reviewed in [1]), and high anti-CMV titres are associated with all-cause and cardiovascular mortality [7,8,9,10]. A high anti-CMV titre has been linked with increased frailty and functional impairment [12,13,14], conflicting reports exist with regard to this association [15]. The anti-CMV titre has been shown to correlate with the T cell proportions [16]

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