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Leukocyte function assessed via serial microlitre sampling of peripheral blood from sepsis patients correlates with disease severity.

ABSTRACT: Dysregulated leukocyte responses underlie the pathobiology of sepsis, which is a leading cause of death. However, measures of leukocyte function are not routinely available in clinical care. Here we report the development and testing of an inertial microfluidic system for the label-free isolation and downstream functional assessment of leukocytes from 50 μl of peripheral blood. We used the system to assess leukocyte phenotype and function in serial samples from 18 hospitalized patients with sepsis and 10 healthy subjects. The sepsis samples had significantly higher levels of CD16^dim and CD16^- neutrophils and CD16⁺ 'intermediate' monocytes, as well as significantly lower levels of neutrophil-elastase release, O₂^- production and phagolysosome formation. Repeated sampling of sepsis patients over 7 days showed that leukocyte activation (measured by isodielectric separation) and leukocyte phenotype and function were significantly more predictive of the clinical course than complete-blood-count parameters. We conclude that the serial assessment of leukocyte function in microlitre blood volumes is feasible and that it provides significantly more prognostic information than leukocyte counting.

SUBMITTER: Jundi B

PROVIDER: S-EPMC6899180 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Leukocyte function assessed via serial microlitre sampling of peripheral blood from sepsis patients correlates with disease severity.

Jundi Bakr B Ryu Hyunryul H Lee Do-Hyun DH Abdulnour Raja-Elie E RE Engstrom Braden D BD Duvall Melody G MG Higuera Angelica A Pinilla-Vera Mayra M Benson Maura E ME Lee Jaemyon J Krishnamoorthy Nandini N Baron Rebecca M RM Han Jongyoon J Voldman Joel J Levy Bruce D BD

Nature biomedical engineering 20191111 12

Dysregulated leukocyte responses underlie the pathobiology of sepsis, which is a leading cause of death. However, measures of leukocyte function are not routinely available in clinical care. Here we report the development and testing of an inertial microfluidic system for the label-free isolation and downstream functional assessment of leukocytes from 50 μl of peripheral blood. We used the system to assess leukocyte phenotype and function in serial samples from 18 hospitalized patients with seps ...[more]

PMID: 31712645

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Project description:BackgroundParkinson's disease is an intractable disorder with heterogeneous clinical presentation that may reflect different underlying pathogenic mechanisms. Surrogate indicators of pathogenic processes correlating with clinical measures may assist in better patient stratification. Mitochondrial function, which is impaired in and central to PD pathogenesis, may represent one such surrogate indicator.MethodsMitochondrial function was assessed by respirometry experiment in fibroblasts derived from idiopathic patients (n = 47) in normal conditions and in experimental settings that do not permit glycolysis and therefore force energy production through mitochondrial function. Respiratory parameters and clinical measures were correlated with bivariate analysis. Machine-learning-based classification and regression trees were used to classify patients on the basis of biochemical and clinical measures. The effects of mitochondrial respiration on α-synuclein stress were assessed monitoring the protein phosphorylation in permitting versus restrictive glycolysis conditions.ResultsBioenergetic properties in peripheral fibroblasts correlate with clinical measures in idiopathic patients, and the correlation is stronger with predominantly nondopaminergic signs. Bioenergetic analysis under metabolic stress, in which energy is produced solely by mitochondria, shows that patients' fibroblasts can augment respiration, therefore indicating that mitochondrial defects are reversible. Forcing energy production through mitochondria, however, favors α-synuclein stress in different cellular experimental systems. Machine-learning-based classification identified different groups of patients in which increasing disease severity parallels higher mitochondrial respiration.ConclusionThe suppression of mitochondrial activity in PD may be an adaptive strategy to cope with concomitant pathogenic factors. Moreover, mitochondrial measures in fibroblasts are potential peripheral biomarkers to follow disease progression. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Dataset Information

Leukocyte function assessed via serial microlitre sampling of peripheral blood from sepsis patients correlates with disease severity.

Publications

Leukocyte function assessed via serial microlitre sampling of peripheral blood from sepsis patients correlates with disease severity.

Similar Datasets

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