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

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

Medicine

Research output: Contribution to journal › Article › peer-review

43 Citations (Scopus)

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.

Original language	English
Pages (from-to)	153-159
Number of pages	7
Journal	Journal of the American Geriatrics Society
Volume	65
Issue number	1
DOIs	https://doi.org/10.1111/jgs.14507
Publication status	Published - Jan 1 2017

Bibliographical note

Funding Information:
The study was supported by the Canadian Institutes of Health Research (CIHR), the Public Health Agency of Canada/CIHR Influenza Research Network (PCIRN), the National Institutes of Health (R01 EB008400/EB/NIBIB), and Natural Sciences and Engineering Research Council of Canada. Dr. Jennie Johnstone received salary support from CIHR while conducting this study. Mark Loeb holds the Michael G. DeGroote Chair in Infectious Diseases at McMaster University. Jonathan Bramson holds a Canadian Research Chair in Translational Cancer Immunology and the John Bienenstock Chair in Molecular Medicine. The authors wish to acknowledge Canada's Michael Smith Genome Sciences Centre, Vancouver, Canada, for use of high-performance computing resources. Conflict of Interest: None. Sponsor's Role: The sponsors had no role in the design, methods, subject recruitment, data collection, analysis and preparation of the manuscript. Author Contributions: Johnstone, McNeil, Fulop, McElhaney, Andrew, Bramson, and Loeb: conceived the study; Parsons, Botelho, Millar, Malek, Brinkman, and Bramson: analyzed the laboratory specimens; Johnstone, Walter, Devereaux, Bramson, and Loeb: analyzed the data; Johnstone: drafted the manuscript and Parsons, Botelho, Millar, McNeil, Fulop, McElhaney, Andrew, Walter, Devereaux, Malek, Brinkman, Bramson, and Loeb provided critical review of the manuscript. Loeb provided funding support for the study.

Publisher Copyright:
© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society

ASJC Scopus Subject Areas

Geriatrics and Gerontology

PubMed: MeSH publication types

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

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10.1111/jgs.14507

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Johnstone, J., Parsons, R., Botelho, F., Millar, J., McNeil, S., Fulop, T., McElhaney, J. E., Andrew, M. K., Walter, S. D., Devereaux, P. J., Malek, M., Brinkman, R. R., Bramson, J., & Loeb, M. (2017). T-Cell Phenotypes Predictive of Frailty and Mortality in Elderly Nursing Home Residents. Journal of the American Geriatrics Society, 65(1), 153-159. https://doi.org/10.1111/jgs.14507

Johnstone, J, Parsons, R, Botelho, F, Millar, J, McNeil, S, Fulop, T, McElhaney, JE, Andrew, MK, Walter, SD, Devereaux, PJ, Malek, M, Brinkman, RR, Bramson, J & Loeb, M 2017, 'T-Cell Phenotypes Predictive of Frailty and Mortality in Elderly Nursing Home Residents', Journal of the American Geriatrics Society, vol. 65, no. 1, pp. 153-159. https://doi.org/10.1111/jgs.14507

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title = "T-Cell Phenotypes Predictive of Frailty and Mortality in Elderly Nursing Home Residents",

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 (na{\"i}ve, 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 na{\"i}ve 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.",

author = "Jennie Johnstone and Robin Parsons and Fernando Botelho and Jamie Millar and Shelly McNeil and Tamas Fulop and McElhaney, {Janet E.} and Andrew, {Melissa K.} and Walter, {Stephen D.} and Devereaux, {P. J.} and Mehrnoush Malek and Brinkman, {Ryan R.} and Jonathan Bramson and Mark Loeb",

note = "Funding Information: The study was supported by the Canadian Institutes of Health Research (CIHR), the Public Health Agency of Canada/CIHR Influenza Research Network (PCIRN), the National Institutes of Health (R01 EB008400/EB/NIBIB), and Natural Sciences and Engineering Research Council of Canada. Dr. Jennie Johnstone received salary support from CIHR while conducting this study. Mark Loeb holds the Michael G. DeGroote Chair in Infectious Diseases at McMaster University. Jonathan Bramson holds a Canadian Research Chair in Translational Cancer Immunology and the John Bienenstock Chair in Molecular Medicine. The authors wish to acknowledge Canada's Michael Smith Genome Sciences Centre, Vancouver, Canada, for use of high-performance computing resources. Conflict of Interest: None. Sponsor's Role: The sponsors had no role in the design, methods, subject recruitment, data collection, analysis and preparation of the manuscript. Author Contributions: Johnstone, McNeil, Fulop, McElhaney, Andrew, Bramson, and Loeb: conceived the study; Parsons, Botelho, Millar, Malek, Brinkman, and Bramson: analyzed the laboratory specimens; Johnstone, Walter, Devereaux, Bramson, and Loeb: analyzed the data; Johnstone: drafted the manuscript and Parsons, Botelho, Millar, McNeil, Fulop, McElhaney, Andrew, Walter, Devereaux, Malek, Brinkman, Bramson, and Loeb provided critical review of the manuscript. Loeb provided funding support for the study. Publisher Copyright: {\textcopyright} 2016, Copyright the Authors Journal compilation {\textcopyright} 2016, The American Geriatrics Society",

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doi = "10.1111/jgs.14507",

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T1 - T-Cell Phenotypes Predictive of Frailty and Mortality in Elderly Nursing Home Residents

AU - Johnstone, Jennie

AU - Parsons, Robin

AU - Botelho, Fernando

AU - Millar, Jamie

AU - McNeil, Shelly

AU - Fulop, Tamas

AU - McElhaney, Janet E.

AU - Andrew, Melissa K.

AU - Walter, Stephen D.

AU - Devereaux, P. J.

AU - Malek, Mehrnoush

AU - Brinkman, Ryan R.

AU - Bramson, Jonathan

AU - Loeb, Mark

N1 - Funding Information: The study was supported by the Canadian Institutes of Health Research (CIHR), the Public Health Agency of Canada/CIHR Influenza Research Network (PCIRN), the National Institutes of Health (R01 EB008400/EB/NIBIB), and Natural Sciences and Engineering Research Council of Canada. Dr. Jennie Johnstone received salary support from CIHR while conducting this study. Mark Loeb holds the Michael G. DeGroote Chair in Infectious Diseases at McMaster University. Jonathan Bramson holds a Canadian Research Chair in Translational Cancer Immunology and the John Bienenstock Chair in Molecular Medicine. The authors wish to acknowledge Canada's Michael Smith Genome Sciences Centre, Vancouver, Canada, for use of high-performance computing resources. Conflict of Interest: None. Sponsor's Role: The sponsors had no role in the design, methods, subject recruitment, data collection, analysis and preparation of the manuscript. Author Contributions: Johnstone, McNeil, Fulop, McElhaney, Andrew, Bramson, and Loeb: conceived the study; Parsons, Botelho, Millar, Malek, Brinkman, and Bramson: analyzed the laboratory specimens; Johnstone, Walter, Devereaux, Bramson, and Loeb: analyzed the data; Johnstone: drafted the manuscript and Parsons, Botelho, Millar, McNeil, Fulop, McElhaney, Andrew, Walter, Devereaux, Malek, Brinkman, Bramson, and Loeb provided critical review of the manuscript. Loeb provided funding support for the study. Publisher Copyright: © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

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

Abstract

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PubMed: MeSH publication types

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