T-Cell Phenotypes Predictive of Frailty and Mortality in Elderly Nursing Home Residents

Jennie Johnstone; Robin Parsons; Fernando Botelho; Jamie Millar; Shelly McNeil; Tamas Fulop; Janet E McElhaney; Melissa K Andrew; Stephen D Walter; P J Devereaux; Mehrnoush Malek; Ryan R Brinkman; Jonathan Bramson; Mark Loeb

doi:10.1111/jgs.14507

T-Cell Phenotypes Predictive of Frailty and Mortality in Elderly Nursing Home Residents

J Am Geriatr Soc. 2017 Jan;65(1):153-159. doi: 10.1111/jgs.14507. Epub 2016 Oct 24.

Authors

Jennie Johnstone^{1

2}, Robin Parsons³, Fernando Botelho³, Jamie Millar³, Shelly McNeil⁴, Tamas Fulop⁵, Janet E McElhaney⁶, Melissa K Andrew⁷, Stephen D Walter¹, P J Devereaux^{1

8}, Mehrnoush Malek⁹, Ryan R Brinkman^{9

10}, Jonathan Bramson^{3

11

12}, Mark Loeb^{1

8

11

12}

Affiliations

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.

PMID: 27775813
DOI: 10.1111/jgs.14507

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.

Keywords: frailty; immune biomarker; immunosenescence; mortality; nursing home.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Age Factors
Aged
Aged, 80 and over
Biomarkers / blood
CD4-Positive T-Lymphocytes / metabolism*
CD8-Positive T-Lymphocytes / metabolism*
Canada / epidemiology
Cohort Studies
Cross-Sectional Studies
Cytomegalovirus / immunology
Female
Frail Elderly*
Humans
Immunosenescence*
Male
Mortality*
Multivariate Analysis
Nursing Homes

Substances

Biomarkers

Abstract

Publication types

MeSH terms

Substances

Grants and funding