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New approach to determine the healthy immune variations by combining clustering methods.

ABSTRACT: Immune-mediated inflammatory diseases are characterized by variability in disease presentation and severity but studying it is a challenging task. Defining the limits of a healthy immune system is therefore a prior step to capture variability in disease conditions. The goal of this study is to characterize the global immune cell composition along with their influencing factors. Blood samples were collected from 2 independent cohorts of respectively 389 (exploratory) and 208 (replication) healthy subjects. Twelve immune cells were measured in blood together with biological parameters. Three complementary clustering approaches were used to evaluate if variability related to the immune cells could be characterized as clusters or as a continuum. Large coefficients of variation confirmed the inter-individual variability of immune cells. Considering all subset variations in an overall analysis, it appeared that the immune makeup was organized as a continuum through the two cohorts. Some intrinsic and environmental factors affected the inter-individual variability of cells but without unveiling separable groups with similar features. This study provides a framework based on complementary clustering approach for analyzing inter-individual variability of immune cells. Our analyses support the absence of clusters in our two healthy cohorts. Also, our study reports some influence of age, gender, BMI, cortisol, season and CMV infection on immune variability.

SUBMITTER: Liefferinckx C

PROVIDER: S-EPMC8076194 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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New approach to determine the healthy immune variations by combining clustering methods.

Liefferinckx Claire C De Grève Zacharie Z Toubeau Jean-François JF Perée Hélène H Quertinmont Eric E Tafciu Vjola V Minsart Charlotte C Rahmouni Souad S Georges Michel M Vallée François F Franchimont Denis D

Scientific reports 20210426 1

Immune-mediated inflammatory diseases are characterized by variability in disease presentation and severity but studying it is a challenging task. Defining the limits of a healthy immune system is therefore a prior step to capture variability in disease conditions. The goal of this study is to characterize the global immune cell composition along with their influencing factors. Blood samples were collected from 2 independent cohorts of respectively 389 (exploratory) and 208 (replication) healthy ...[more]

PMID: 33903641

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Project description:Per- and polyfluoroalkyl substances (PFAS) are a very large (thousands of chemicals) category; these substances have important industrial and consumer product applications. PFAS are highly persistent in the environment, and some are known to pose human health hazard. Regulatory agencies worldwide are considering restrictions and outright bans of PFAS; however, little data exists to make informed decisions. Therefore, a prioritization strategy is urgently needed for evaluation of potential hazards of PFAS. Structure-based grouping could expedite selection of PFAS for testing; still, the hypothesis that structure-effect relationships exist requires confirmation. We tested 26 structurally diverse PFAS from 8 groups in two human cell types from organs that are thought to be targets for PFAS. We used human induced pluripotent stem cell-derived hepatocytes and cardiomyocytes and tested concentration-response effects on both cell function and gene expression. Few phenotypic effects were observed in hepatocytes, but negative chronotropy was observed for 8 of 26 PFAS. Substance- and cell-dependent transcriptomic changes were more pronounced; however, little evidence of group-specific effects was observed. In hepatocytes, we found up-regulation of stress-related and extracellular matrix organization pathways, and down-regulation of fat metabolism. In cardiomyocytes, contractility-related pathways were most affected. Using these data, we derived phenotypic and transcriptomic point of departure estimates and compared them to predicted PFAS exposures. The conservative estimates for bioactivity and exposure were used to derive margin-of-exposure (MOE) for each PFAS. We found that most (23 of 26) PFAS had MOE>1. Overall, our data suggests that chemical structure-based grouping of PFAS may not be an appropriate strategy to predict their biological effects. This means that testing of the individual PFAS would be needed for confident decision-making. Our proposed strategy of using two human cell types and considering both phenotypic and transcriptomic effects, combined with dose-response analysis, may be used for prioritization of PFAS.

Project description:BackgroundIncreases in human longevity have made it critical to distinguish healthy longevity from longevity without regard to health. Current methods focus on expectations of healthy longevity, and are often limited to binary health outcomes (e.g., disabled vs. not disabled). We present a new matrix formulation for the statistics of healthy longevity, based on health prevalence data and Markov chain theory, applicable to any kind of health outcome and which provides variances and higher moments as well as expectations of healthy life.MethodThe model is based on a Markov chain description of the life course coupled with the moments of health outcomes ("rewards") at each age or stage. As an example, we apply the method to nine European countries using the SHARE survey data on the binary outcome of disability as measured by activities of daily living, and the continuous health outcome of hand grip strength.ResultsWe provide analytical formulas for the mean, variance, coefficient of variation, skewness and other statistical properties of healthy longevity. The analysis is applicable to binary, categorical, ordinal, or interval scale health outcomes. The results are easily evaluated in any matrix-oriented software. The SHARE results reveal familiar patterns for the expectation of life and of healthy life: women live longer than men but spend less time in a healthy condition. New results on the variance shows that the standard deviation of remaining healthy life declines with age, but the coefficient of variation is nearly constant. Remaining grip strength years decrease with age more dramatically than healthy years but their variability pattern is similar to the pattern of healthy years. Patterns are similar across nine European countries.ConclusionsThe method extends, in several directions, current calculations of health expectancy (HE) and disability-adjusted life years (DALYs). It applies to both categorical and continuous health outcomes, to combinations of multiple outcomes (e.g., death and disability in the formulation of DALYs) and to age- or stage-classified models. It reveals previously unreported patterns of variation among individuals in the outcomes of healthy longevity.

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New approach to determine the healthy immune variations by combining clustering methods.

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New approach to determine the healthy immune variations by combining clustering methods.

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