Jennie Johnstone1,2, Robin Parsons3, Fernando Botelho3, Jamie Millar3, Shelly McNeil4, Tamas Fulop5, Janet E McElhaney6, Melissa K Andrew7, Stephen D Walter1, P J Devereaux1,8, Mehrnoush Malek9, Ryan R Brinkman9,10, Jonathan Bramson3,11,12, Mark Loeb1,8,11,12. 1. Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada. 2. Public Health Ontario, Toronto, Ontario, Canada. 3. McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada. 4. Canadian Center for Vaccinology, IWK Health Center and Capital Health, Dalhousie University, Halifax, Nova Scotia, Canada. 5. Department of Medicine, Geriatrics Division, Research Center on Aging, University of Sherbrooke, Sherbrooke, Quebec, Canada. 6. Health Sciences North Research Institute, Sudbury, Ontario, Canada. 7. Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada. 8. Department of Medicine, McMaster University, Hamilton, Ontario, Canada. 9. Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada. 10. Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada. 11. Department Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada. 12. Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
Abstract
OBJECTIVES: To determine whether immune phenotypes associated with immunosenescence are predictive of frailty and mortality within 1-year in elderly nursing home residents. DESIGN: Cross sectional study of frailty; prospective cohort study of mortality. SETTING: Thirty-two nursing homes in four Canadian cities between September 2009 and October 2011. PARTICIPANTS: Nursing home residents aged 65 and older (N = 1,072, median age 86, 72% female). MEASUREMENTS: After enrollment, peripheral blood mononuclear cells were obtained and analyzed using flow cytometry for CD4+ and CD8+ T-cell subsets (naïve, memory (central, effector, terminally differentiated, senescent), and regulatory T-cells) and cytomegalovirus (CMV)-reactive CD4+ and CD8+ T-cells. Multilevel linear regression analysis was performed to determine the relationship between immune phenotypes and frailty; frailty was measured at the time of enrollment using the Frailty Index. A Cox proportional hazards model was used to determine the relationship between immune phenotypes and time to death (within 1 year). RESULTS: Mean Frailty Index was 0.44 ± 0.13. Multilevel regression analysis showed that higher percentages of naïve CD4+ T-cells (P = .001) and effector memory CD8+ T-cells (P = .02) were associated with a lower mean Frailty Index, whereas a higher percentage of CD8+ central memory T-cells was associated with a higher mean Frailty Index score (P = .02). One hundred fifty one (14%) members of the cohort died within 1 year. Multivariable analysis showed a significant negative multiplicative interaction between age and percentage of CMV-reactive CD4+ T-cells (hazard ratio = 0.87, 95% confidence interval = 0.79-0.96). No other significant factors were identified. CONCLUSION: Immune phenotypes found to be predictive of frailty and mortality in this study can help further understanding of immunosenescence and may provide a rationale for future intervention studies designed to modulate immunity.
OBJECTIVES: To determine whether immune phenotypes associated with immunosenescence are predictive of frailty and mortality within 1-year in elderly nursing home residents. DESIGN: Cross sectional study of frailty; prospective cohort study of mortality. SETTING: Thirty-two nursing homes in four Canadian cities between September 2009 and October 2011. PARTICIPANTS: Nursing home residents aged 65 and older (N = 1,072, median age 86, 72% female). MEASUREMENTS: After enrollment, peripheral blood mononuclear cells were obtained and analyzed using flow cytometry for CD4+ and CD8+ T-cell subsets (naïve, memory (central, effector, terminally differentiated, senescent), and regulatory T-cells) and cytomegalovirus (CMV)-reactive CD4+ and CD8+ T-cells. Multilevel linear regression analysis was performed to determine the relationship between immune phenotypes and frailty; frailty was measured at the time of enrollment using the Frailty Index. A Cox proportional hazards model was used to determine the relationship between immune phenotypes and time to death (within 1 year). RESULTS: Mean Frailty Index was 0.44 ± 0.13. Multilevel regression analysis showed that higher percentages of naïve CD4+ T-cells (P = .001) and effector memory CD8+ T-cells (P = .02) were associated with a lower mean Frailty Index, whereas a higher percentage of CD8+ central memory T-cells was associated with a higher mean Frailty Index score (P = .02). One hundred fifty one (14%) members of the cohort died within 1 year. Multivariable analysis showed a significant negative multiplicative interaction between age and percentage of CMV-reactive CD4+ T-cells (hazard ratio = 0.87, 95% confidence interval = 0.79-0.96). No other significant factors were identified. CONCLUSION: Immune phenotypes found to be predictive of frailty and mortality in this study can help further understanding of immunosenescence and may provide a rationale for future intervention studies designed to modulate immunity.
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