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

2020 ◽  
Author(s):  
Leonard Daniël Samson ◽  
A. Mieke H. Boots ◽  
José A. Ferreira ◽  
H. Susan J. Picavet ◽  
Lia G. H. De Rond ◽  
...  

Abstract 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. Thus, our aim in this exploratory study was to investigate whether frailty is associated with changes in immune cell subpopulations and whether associations differ between men and women. Therefore, we performed in-depth immune cell phenotyping by enumerating a total of 37 subsets 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 an association study, frailty was observed to be associated with increases in numbers of neutrophils in both men and in women. Furthermore, sex-specific associations were found. Frailer women, but not men, showed higher numbers of total and CD16^-^ monocytes and lower numbers of CD56^+^ T cells. Overall, the accuracy of the predictions in the random forest analysis was low (9.2% explained variance in men and 12.2% in women). Yet, the random forest analysis confirmed all associations mentioned above, but did not confirm a possible negative association in women between frailty and late differentiated CD4^+^ TemRA cells. Moreover, the random forest analysis revealed additional relationships with frailty, with frailer men showing higher CD16^+^ monocyte and lower naïve B cell numbers. Other important variables for predicting frailty were plasmablast numbers in men and total T cell numbers in women. Conclusions: We report on observed associations of frailty with elevated myeloid cell numbers in men and women. In-depth immune cellular profiling also revealed sex-specific associations of frailty with several immune subpopulations. However, an expected positive association between frailty and memory T cells was not observed. We hope that our study will prompt further investigation into the immune mechanisms associated with the development of frailty in men and women.

2020 ◽  
Author(s):  
Leonard Daniël Samson ◽  
A. Mieke H. Boots ◽  
José A. Ferreira ◽  
H. Susan J. Picavet ◽  
Lia G. H. de Rond ◽  
...  

Abstract 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. Thus, our aim in this exploratory study was to investigate whether frailty is associated with changes in immune cell subpopulations and whether associations differed between men and women. Therefore, we performed in-depth immune cell phenotyping by enumerating subsets 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: Frailty was observed to be associated with numerical increases in neutrophils in men and in women. Furthermore, sex-specific associations were found with frailer men, but not women, showing higher numbers of non-classical monocytes and transitional B cells. In addition, frailer women, but not men, showed higher numbers of classical monocytes and lower numbers of NK-T cells. Interestingly, we did not detect an association between frailty and late differentiated memory T-cell subsets. Although the accuracy of the predictions of frailty from information on the immune subpopulations was low (10.7% explained variance in men and 10.5% in women), the prediction model confirmed our findings in the association study. Conclusions: We here report on observed associations of frailty with elevated neutrophil numbers, but not with late stage memory T cell subsets. Furthermore, in-depth immune cellular profiling revealed sex specific associations of frailty with several immune subpopulations. We hope that our study will prompt further investigation into the immune mechanisms associated with the development of frailty in men and women.


2021 ◽  
Vol 10_2021 ◽  
pp. 93-102
Author(s):  
Korotkova T.D. Korotkova ◽  
Krechetova L.V. Krechetova ◽  
Inviyaeva E.V. Inviyaeva ◽  
Vtorushina V.V. Vtorushina V ◽  
Vanko L.V. Vanko ◽  
...  

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ao Liu ◽  
Kangni Jia ◽  
Huaibin Liang ◽  
Qi Jin

Abstract Background The development of atrial fibrillation (AF) following valvular heart disease (VHD) remains a common disease and is associated with substantial adverse complications. However, valid molecular diagnostic and therapeutic tools for post-VHD AF have not been fully established. This study was conducted to discover the molecular mechanisms and immune microenvironment underlying AF following VHD. Methods Gene expression profiles of the GSE41177 dataset were assessed to construct a protein–protein interaction network, and then, autophagy-related hub genes were identified. In addition, to determine the functions of immune cell infiltration in valvular AF, we used the CIBERSORT algorithm to estimate the composition of 22 immune cell types in valvular heart disease. Finally, correlation analysis was carried out to identify the relationship between differentially expressed autophagy-related genes (DEARGs) and significant immune cell subpopulations to reveal potential regulatory pathways. Results A total of 153 DEARGs were identified in AF-VHD patients compared with controlled donors. Moreover, we screened the top ten hub nodes with the highest degrees through a network analysis. The ten hub nodes were considered hub genes related to AF genesis and progression. Then, we revealed six significant immune cell subpopulations through the CIBERSORT algorithm. Finally, correlation analysis was performed, and six DEARGs (BECN1, GAPDH, ATG7, MAPK3, BCL2L1, and MYC) and three immune cell subpopulations (T cells CD4 memory resting, T cells follicular helper, and neutrophils) were identified as the most significant potential regulators. Conclusion The DEARGs and immune cells identified in our study may be critical in AF development following VHD and provide potential predictive markers and therapeutic targets for determining a treatment strategy for AF patients.


2016 ◽  
Vol 72 (3) ◽  
pp. 531-534 ◽  
Author(s):  
H. Al-Khalifa ◽  
A. Al-Nasser ◽  
M. Al-Bahouh ◽  
G. Ragheb ◽  
S. Al-Qalaf ◽  
...  

2021 ◽  
pp. jim-2021-001788
Author(s):  
Xiumei Liu ◽  
Xueming Wang ◽  
Xiaoling Zhang ◽  
Ai hua Cao

Tic disorders (TD) are childhood-onset neurological disorders. Immune system dysregulation has been postulated to play a role in TD, and its mechanisms likely involve dysfunctional neural-immune cross-talk, which ultimately leads to altered maturation of the brain pathways that control different TD clinical manifestations and behavioral and emotional damages. Clinical studies have demonstrated an association between TD and allergies and overactive immune responses at a systemic level. In this study, the Yale Global Tic Severity Scale was taken as a global measure of tic severity. Compared with the control group, the group of children with TD plus allergic diseases displayed significantly increased Yale total scores (p<0.05), which suggests that children with TD plus allergic diseases have heavier tic symptoms. Both motor and vocal tic scores are higher in the group of children with TD plus allergy compared with the control group. We counted immune cell subpopulations using FACS. T lymphocyte subset comparison of CD3, CD4, CD8, and CD4:CD8 expression ratios revealed that the level of CD3, CD4, and CD4:CD8 in children with TD plus allergic diseases was significantly lower than those of children with TD without allergic diseases. These differences were statistically significant (p<0.05) and suggest that children with TD plus allergic diseases have imbalanced T lymphocyte subsets. We concluded that allergy increased the severity of TD through an imbalance in cellular immunity. Studies need to be done to show whether treatment of allergic symptoms leads to a decrease in TD manifestations.


2016 ◽  
Vol 197 (2) ◽  
pp. 665-673 ◽  
Author(s):  
Pingzhang Wang ◽  
Wenling Han ◽  
Dalong Ma

2020 ◽  
Vol 9 (24) ◽  
Author(s):  
Katharine A. Kott ◽  
Stephen T. Vernon ◽  
Thomas Hansen ◽  
Macha de Dreu ◽  
Souvik K. Das ◽  
...  

Abstract Coronary artery disease remains the leading cause of death globally and is a major burden to every health system in the world. There have been significant improvements in risk modification, treatments, and mortality; however, our ability to detect asymptomatic disease for early intervention remains limited. Recent discoveries regarding the inflammatory nature of atherosclerosis have prompted investigation into new methods of diagnosis and treatment of coronary artery disease. This article reviews some of the highlights of the important developments in cardioimmunology and summarizes the clinical evidence linking the immune system and atherosclerosis. It provides an overview of the major serological biomarkers that have been associated with atherosclerosis, noting the limitations of these markers attributable to low specificity, and then contrasts these serological markers with the circulating immune cell subtypes that have been found to be altered in coronary artery disease. This review then outlines the technique of mass cytometry and its ability to provide high‐dimensional single‐cell data and explores how this high‐resolution quantification of specific immune cell subpopulations may assist in the diagnosis of early atherosclerosis in combination with other complimentary techniques such as single‐cell RNA sequencing. We propose that this improved specificity has the potential to transform the detection of coronary artery disease in its early phases, facilitating targeted preventative approaches in the precision medicine era.


Sign in / Sign up

Export Citation Format

Share Document