Immune cell phenotypes and mortality in the Framingham Heart Study.

IF 5.2 2区医学 Q1 GERIATRICS & GERONTOLOGY

Immunity & Ageing Pub Date : 2024-06-12 DOI:10.1186/s12979-024-00431-6

Ahmed A Y Ragab, Margaret F Doyle, Jiachen Chen, Yuan Fang, Kathryn L Lunetta, Joanne M Murabito

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引用次数: 0

Abstract

Background: Global life expectancy is rising, with the 60 + age group projected to hit 2 billion by 2050. Aging impacts the immune system. A notable marker of immune system aging is the presence of Aging-Related Immune Cell Phenotypes (ARIPs). Despite their importance, links between immune cell phenotypes including ARIPs and mortality are underexplored. We prospectively investigated 16 different immune cell phenotypes using flow cytometry and IL-6 in relation to survival outcome among dementia-free Framingham Heart Study (FHS) offspring cohort participants who attended the seventh exam (1998-2001).

Results: Among 996 participants (mean age 62 years, range 40 to 88 years, 52% female), the 19-year survival rate was 65%. Adjusting for age, sex, and cytomegalovirus (CMV) serostatus, higher CD4/CD8 and Tc17/CD8 + Treg ratios were significantly associated with lower all-cause mortality (HR: 0.86 [0.76-0.96], 0.84 [0.74-0.94], respectively), while higher CD8 regulatory cell levels (CD8 + CD25 + FoxP3 +) were associated with increased all-cause mortality risk (HR = 1.17, [1.03-1.32]). Elevated IL-6 levels correlated with higher all-cause, cardiovascular, and non-cardiovascular mortality (HR = 1.43 [1.26-1.62], 1.70 [1.31-2.21], and 1.36 [1.18-1.57], respectively). However, after adjusting for cardiovascular risk factors and prevalent cancer alongside age, sex, and CMV, immune cell phenotypes were no longer associated with mortality in our cohort. Nonetheless, IL-6 remained significantly associated with all-cause and cardiovascular mortality (HRs: 1.3 [1.13-1.49], 1.5 [1.12-1.99], respectively).

Conclusions: In 19-year follow-up, higher Tc17/CD8 + Treg and CD4/CD8 ratios were associated with lower all-cause mortality, while the CD8 + CD25 + FoxP3 + (CD8 + Treg) phenotype showed increased risk. Elevated IL-6 levels consistently correlated with amplified mortality risks. These findings highlight the links between immune phenotypes and mortality, suggesting implications for future research and clinical considerations.

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弗雷明汉心脏研究中的免疫细胞表型和死亡率。

背景：全球人口的预期寿命正在延长，预计到 2050 年，60 岁以上的人口将达到 20 亿。衰老会影响免疫系统。免疫系统衰老的一个显著标志是出现与衰老相关的免疫细胞表型（ARIPs）。尽管ARIPs非常重要，但包括ARIPs在内的免疫细胞表型与死亡率之间的联系却未得到充分探索。我们使用流式细胞仪和 IL-6 对参加第七次检查（1998-2001 年）的无痴呆症的弗雷明汉心脏研究（FHS）后代队列参与者中 16 种不同的免疫细胞表型与生存结果的关系进行了前瞻性研究：在996名参与者（平均年龄62岁，年龄范围40-88岁，52%为女性）中，19年存活率为65%。调整年龄、性别和巨细胞病毒（CMV）血清状态后，CD4/CD8 和 Tc17/CD8 + Treg 比率越高，全因死亡率越低（HR：分别为 0.86 [0.76-0.96]、0.84 [0.74-0.94]），而 CD8 调节细胞水平越高（CD8 + CD25 + FoxP3 +），全因死亡风险越高（HR = 1.17，[1.03-1.32]）。IL-6 水平升高与全因、心血管和非心血管死亡率升高相关（HR = 1.43 [1.26-1.62]、1.70 [1.31-2.21] 和 1.36 [1.18-1.57]）。然而，在调整了心血管风险因素和流行性癌症以及年龄、性别和 CMV 后，我们队列中的免疫细胞表型不再与死亡率相关。然而，IL-6仍与全因死亡率和心血管死亡率显著相关（HRs：分别为1.3 [1.13-1.49]、1.5 [1.12-1.99]）：在19年的随访中，较高的Tc17/CD8 + Treg和CD4/CD8比率与较低的全因死亡率相关，而CD8 + CD25 + FoxP3 + (CD8 + Treg)表型则显示风险增加。IL-6水平的升高与死亡率风险的增加一直相关。这些发现凸显了免疫表型与死亡率之间的联系，为今后的研究和临床考虑提供了参考。

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来源期刊

Immunity & Ageing GERIATRICS & GERONTOLOGY-IMMUNOLOGY

CiteScore

10.20

自引率

3.80%

发文量

期刊介绍： Immunity & Ageing is a specialist open access journal that was first published in 2004. The journal focuses on the impact of ageing on immune systems, the influence of aged immune systems on organismal well-being and longevity, age-associated diseases with immune etiology, and potential immune interventions to increase health span. All articles published in Immunity & Ageing are indexed in the following databases: Biological Abstracts, BIOSIS, CAS, Citebase, DOAJ, Embase, Google Scholar, Journal Citation Reports/Science Edition, OAIster, PubMed, PubMed Central, Science Citation Index Expanded, SCImago, Scopus, SOCOLAR, and Zetoc.