Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
Public Health Ontario, Toronto, Ontario, Canada.
J Am Geriatr Soc. 2017 Jan;65(1):153-159. doi: 10.1111/jgs.14507. Epub 2016 Oct 24.
To determine whether immune phenotypes associated with immunosenescence are predictive of frailty and mortality within 1-year in elderly nursing home residents.
Cross sectional study of frailty; prospective cohort study of mortality.
Thirty-two nursing homes in four Canadian cities between September 2009 and October 2011.
Nursing home residents aged 65 and older (N = 1,072, median age 86, 72% female).
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).
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.
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.
确定与免疫衰老相关的免疫表型是否可预测老年人在疗养院居住者 1 年内的脆弱和死亡。
脆弱性的横断面研究;死亡率的前瞻性队列研究。
2009 年 9 月至 2011 年 10 月间加拿大四个城市的 32 个疗养院。
65 岁及以上的疗养院居住者(N=1072 人,中位年龄 86 岁,72%为女性)。
入组后,获取外周血单核细胞,并用流式细胞术分析 CD4 和 CD8 T 细胞亚群(幼稚、记忆(中央、效应、终末分化、衰老)和调节性 T 细胞)和巨细胞病毒(CMV)反应性 CD4 和 CD8 T 细胞。采用多水平线性回归分析确定免疫表型与脆弱性之间的关系;使用脆弱指数在入组时测量脆弱性。采用 Cox 比例风险模型确定免疫表型与 1 年内死亡(死亡时间)之间的关系。
平均脆弱指数为 0.44±0.13。多水平回归分析显示,幼稚 CD4 T 细胞(P=0.001)和效应记忆 CD8 T 细胞(P=0.02)的百分比较高与较低的平均脆弱指数相关,而 CD8 中央记忆 T 细胞的百分比较高与较高的平均脆弱指数评分相关(P=0.02)。队列中有 151 名(14%)成员在 1 年内死亡。多变量分析显示年龄和 CMV 反应性 CD4 T 细胞百分比之间存在显著的负相乘交互作用(危险比=0.87,95%置信区间=0.79-0.96)。未发现其他显著因素。
本研究中发现与脆弱性和死亡率相关的免疫表型有助于进一步了解免疫衰老,并可能为旨在调节免疫的未来干预研究提供依据。