Frailty in Older Adults Is Associated With Plasma Concentrations of Inflammatory Mediators but Not With Lymphocyte Subpopulations

Marcos-Pérez, Diego; Sánchez-Flores, María; Maseda, Ana; Lorenzo-López, Laura; Millán-Calentí, José Carlos; Gostner, Johanna M.; Fuchs, Dietmar; Pásaro, Eduardo; Laffón, Blanca; Valdiglesias, Vanessa

doi:10.3389/fimmu.2018.01056

Cited by 88 publications

(72 citation statements)

References 51 publications

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“…Our data support past studies that have identified the biological underpinnings of frailty as one of immune activation, with effects that linger into the early posttransplant time frame . There is substantial evidence pointing to frailty as a heightened inflammatory state, and biomarkers, such as sTNF‐RII, have even been found to be predictive of frailty status . These past findings of immune activation in frail patients are consistent with our observation of increased rates of ACR among this cohort of patients.…”

Section: Discussionsupporting

confidence: 91%

Frailty Is Associated With Increased Rates of Acute Cellular Rejection Within 3 Months After Liver Transplantation

et al. 2020

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Frailty, a state of decreased physiological reserve, has been associated with dysregulation of the immune system. We hypothesized that frailty is associated with differential rates of acute cellular rejection (ACR) in liver transplantation (LT) recipients. Our study included LT recipients from 2014 to 2016 who had a pre‐LT frailty assessment using the liver frailty index (LFI). Frailty was defined as an LFI ≥4.5. ACR at 3 months was ascertained from pathology reports, and immunosuppression regimens were collected from chart review. There were 241 LT recipients who were included: 46 (19%) were classified as frail before LT. Median tacrolimus trough levels, mycophenolate doses, and corticosteroid doses at discharge and 3 months were similar between frail and nonfrail patients. Within 3 months after LT, 7 (15%) frail patients versus 10 (5%) nonfrail patients experienced ACR (P = 0.02). In the univariate analysis, frailty was associated with a higher odds of ACR at 3 months (OR, 3.3; 95% confidence interval, 1.2‐9.3; P = 0.02). Bivariate analyses were conducted with covariates that were associated with ACR in the univariate analysis or that were previously associated with either frailty (age and female sex) or ACR (Model for End‐Stage Liver Disease score and ascites), as well as relevant immunosuppression variables. In the bivariate analyses, frailty remained significantly associated with ACR at 3 months with an odds ratio relatively similar to the unadjusted value. In conclusion, frailty is associated with an increased rate of ACR within 3 months, despite similar immunosuppression regimens, suggesting that frailty should be considered in immediate post‐LT management.

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Section: Discussionsupporting

confidence: 91%

Frailty Is Associated With Increased Rates of Acute Cellular Rejection Within 3 Months After Liver Transplantation

et al. 2020

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“…Low lymphocyte counts predicted the progression with frailty and this effect has been linked to a deterioration of muscular activity, which is traditionally involved in the physiopathology of frailty syndrome [63,64]. Several studies support the association between lymphopenia and inflammation/immunosuppression, which are both crucial mechanisms linked to frailty [65,66]. A recent observational prospective single-center study in patients with coronary disease showed that in multivariate analysis, lymphocyte counts were inversely related to the odds of frailty, with an exponential increase in risk [66].…”

Section: Discussionmentioning

confidence: 99%

Interleukin-6 and Lymphocyte Count Associated and Predicted the Progression of Frailty Syndrome in Prostate Cancer Patients Undergoing Antiandrogen Therapy

Buigues

Navarro-Martínez

Sánchez-Martínez

et al. 2020

Cancers

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Frailty syndrome is a functional state that includes a loss of ability to react to stressors, and is associated with poor outcomes, morbidity and premature mortality. The first line treatment in many men with prostate cancer (PCa) consists of an androgen-deprivation therapy (ADT) which can promote or favor frailty syndrome and ADT may therefore favor the progression of frailty over time. Among the pathophysiological bases of frailty, the presence of chronic low-grade inflammation has been associated with its adverse outcomes, but longitudinal studies are needed to validate these biomarkers. In this study, we prospectively evaluate frailty syndrome and blood inflammatory markers (IL1-beta, IL-6, IL-8, TNF alpha, C reactive protein) and leukocytes were measured at baseline and an average of 1 year later in PCa under ADT. Frailty was defined as having three or more of the following components: low lean mass, weakness, self-reported exhaustion, low activity level, and slow walking speed; prefrailty was defined as having one or two of those components. Multinomial regression analysis showed that among the inflammatory biomarkers, those significantly and repeatedly (baseline and follow-up time points) (p < 0.05) associated with frailty syndrome were high IL-6 levels and low lymphocyte counts in blood. Other biomarkers such as IL-8, monocyte counts and C reactive protein were significantly associated with frailty syndrome (p < 0.05) in cross-sectional analyses, but they do not predict frailty progression at 1 year-follow-up. Receiver operating characteristic curve analysis showed that both lymphocyte counts and IL-6 concentration significantly (p < 0.05) (although moderately) discriminate PCa patients that progressed in the severity of frailty syndrome. IL-6 and lymphocytes count are possible biomarkers, useful for identifying frail patients and predicting the progression of frailty in PCa under ADT. Our study suggests the use of these biomarkers to guide clinical decisions on prostate cancer treatment based on a multidisciplinary approach.

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“…However, it is largely unknown how changes in the immune cellular composition differ between individuals who age in good health from those who become frail at a relatively early age. Several studies have been performed on this subject, but some of these were done in the extreme elderly of 85 years old or above [5], while others focused on a limited set of lymphocyte phenotypes [6][7][8]. Importantly, few studies have been performed enumerating a comprehensive set of immune phenotypes in freshly drawn whole blood samples.…”

Section: Introductionmentioning

confidence: 99%

In-depth immune cellular profiling reveals sex-specific associations with frailty

et al. 2020

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Background: With advancing age, the composition of leukocyte subpopulations in peripheral blood is known to change, but how this change differs between men and women and how it relates to frailty is poorly understood. Our aim in this exploratory study was to investigate whether frailty is associated with changes in immune cell subpopulations and whether this differs between men and women. Therefore, we performed in-depth immune cellular profiling by enumerating a total of 37 subpopulations of T cells, B cells, NK cells, monocytes, and neutrophils in peripheral blood of 289 elderly people between 60-87 years of age. Associations between frailty and each immune cell subpopulation were tested separately in men and women and were adjusted for age and CMV serostatus. In addition, a random forest algorithm was used to predict a participant's frailty score based on enumeration of immune cell subpopulations. Results: In the association study, frailty was found to be associated with increased numbers of neutrophils in both men and in women. Frailer women, but not men, showed higher numbers of total and CD16monocytes, and lower numbers of both CD56 + T cells and late differentiated CD4 + TemRA cells. The random forest algorithm confirmed all the findings of the association studies in men and women. In men, the predictive accuracy of the algorithm was too low (5.5%) to warrant additional conclusions on top of the ones derived from the association study. In women however, the predictive accuracy was higher (23.1%), additionally revealing that total T cell numbers and total lymphocyte numbers also contribute in predicting frailty. Conclusions: In-depth immune cellular profiling revealed consistent associations of frailty with elevated numbers of myeloid cell subpopulations in both men and women. Furthermore, additional associations were found between frailty and lower numbers of some T cell subpopulations, in women only. Thus, our study indicates sex-specific associations of immune subpopulations with frailty. We hope that our study will prompt further investigation into the sex-specific immune mechanisms associated with the development of frailty.

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Frailty in Older Adults Is Associated With Plasma Concentrations of Inflammatory Mediators but Not With Lymphocyte Subpopulations

Cited by 88 publications

References 51 publications

Frailty Is Associated With Increased Rates of Acute Cellular Rejection Within 3 Months After Liver Transplantation

Frailty Is Associated With Increased Rates of Acute Cellular Rejection Within 3 Months After Liver Transplantation

Interleukin-6 and Lymphocyte Count Associated and Predicted the Progression of Frailty Syndrome in Prostate Cancer Patients Undergoing Antiandrogen Therapy

In-depth immune cellular profiling reveals sex-specific associations with frailty

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