Immune Predictors of Clinical Outcomes in Elderly Nursing Home Residents

Abstract

Elderly residents of nursing homes are at high risk of respiratory viral infection, mortality and frailty. It is a widely held view that the dysfunctional changes to the immune system that arise from ageing, known as immunosenescence are responsible for the increased risk of infection, mortality and frailty; however only sparse data exist to substantiate this. Furthermore, the majority of studies investigating these associations have excluded elderly nursing home residents, thus little is known about immune phenotypes in this group. In this thesis, I first characterized immune phenotypes in elderly nursing home residents by comparing immune phenotypes in an elderly nursing home cohort to a group of younger healthy adults. I then explored how age, sex, frailty and nutrition influence immune phenotypes in the elderly group. I subsequently used different statistical analyses, including Cox proportional hazards modeling, hierarchical cluster analysis and multi-level modelling to identifying immune biomarkers predictive of clinical outcomes in elderly nursing home residents including respiratory viral infection, mortality and frailty. We found that high cytomegalovirus (CMV)-reactive CD4+ T-cells were associated with an increased risk of respiratory viral infection and high T-regulatory cells (T-regs) were associated with a reduced risk of respiratory viral infection. High CMV-reactive CD4+ T-cells were also associated with an increased risk of mortality within the subsequent 1-year in those aged 65-84 years but had no differential effect in those aged 85-104 years. Other immune phenotypes were not predictive of mortality. Higher naïve CD4+ T-cells and effector memory CD8+ T-cells predicted lower levels of frailty and higher central memory CD8+ T-cells predicted higher levels of frailty. These findings may help provide more focused care through targeted prevention. Furthermore, knowledge of these immune biomarkers provides insight into how immunosenescence may contribute to these clinical outcomes and will help guide future research into novel prevention strategies.