Low-Density Granulocytes are a novel immunopathological feature in both Multiple Sclerosis and Neuromyelitis optica spectrum disorder

Ostendorf, Lennard; Mothes, Ronja; Köppen, S.; Lindquist, Randall L.; Bellmann‐Strobl, Judith; Asseyer, Susanna; Ruprecht, Klemens; Niesner, Raluca; Hauser, Anja E.; Paul, Friedemann; Radbruch, Helena

doi:10.1101/668160

Cited by 9 publications

(9 citation statements)

References 10 publications

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“…Granulocytes, such as neutrophils and eosinophils, are normally excluded from the PBMC fraction following density gradient separation. However, low-density granulocytes are found in the PBMC layer of peripheral blood collected from patients with inflammatory diseases 14 . In patients with COVID-19, increases in monocytes, low-density neutrophils and eosinophils correlated with the severity of disease (Fig.…”

Section: Immunological Features Of Covid-19mentioning

confidence: 99%

Longitudinal analyses reveal immunological misfiring in severe COVID-19

Lucas

Wong

Klein

et al. 2020

Nature

1,951

209

2,204

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Recent studies have provided insights into the pathogenesis of coronavirus disease 2019 (COVID-19) 1 – 4 . However, the longitudinal immunological correlates of disease outcome remain unclear. Here we serially analysed immune responses in 113 patients with moderate or severe COVID-19. Immune profiling revealed an overall increase in innate cell lineages, with a concomitant reduction in T cell number. An early elevation in cytokine levels was associated with worse disease outcomes. Following an early increase in cytokines, patients with moderate COVID-19 displayed a progressive reduction in type 1 (antiviral) and type 3 (antifungal) responses. By contrast, patients with severe COVID-19 maintained these elevated responses throughout the course of the disease. Moreover, severe COVID-19 was accompanied by an increase in multiple type 2 (anti-helminths) effectors, including interleukin-5 (IL-5), IL-13, immunoglobulin E and eosinophils. Unsupervised clustering analysis identified four immune signatures, representing growth factors (A), type-2/3 cytokines (B), mixed type-1/2/3 cytokines (C), and chemokines (D) that correlated with three distinct disease trajectories. The immune profiles of patients who recovered from moderate COVID-19 were enriched in tissue reparative growth factor signature A, whereas the profiles of those with who developed severe disease had elevated levels of all four signatures. Thus, we have identified a maladapted immune response profile associated with severe COVID-19 and poor clinical outcome, as well as early immune signatures that correlate with divergent disease trajectories.

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Section: Immunological Features Of Covid-19mentioning

confidence: 99%

Longitudinal analyses reveal immunological misfiring in severe COVID-19

Lucas

Wong

Klein

et al. 2020

Nature

1,951

209

2,204

View full text Add to dashboard Cite

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“…NET formation also correlated with age and was lowest in younger persons. The risk of thrombosis also increases with age and neutrophils of individuals at younger age might be less prone to prothrombotic NET formation.Data on LDN frequency in healthy controls are rarely available and LDN counts vary between reports(24,25). HDN and LDN counts showed no age related differences, however, percentages of mature CD62L high /CD16 high LDNs correlated negatively and percentage of newly released CD16 low LDNs positively with age.…”

mentioning

confidence: 93%

WITHDRAWN: Age-related changes of neutrophil characteristics, potential of activation, DNA release and NET formation

Krall

Mauracher

Roiß

et al. 2020

Preprint

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Background: Neutrophils are a heterogeneous population of leukocytes, which can be subdivided into high and low density neutrophils (HDNs/LDNs). They are known to fight intruders with different mechanisms, including the release of neutrophil extracellular traps (NETs), which have also been associated with thrombosis. Risk of both, thrombosis and infections, increase with age. Differences in neutrophil subpopulations and functionality have been shown in various disease states, but investigations in healthy subjects and their dependence on age are lacking. The aim of this study was to investigate age-related changes in neutrophils regarding neutrophil subpopulations, their potential of activation, DNA release and NET formation. Methods: Neutrophil subpopulations (HDNs and LDNs) were isolated from 25 healthy individuals subdivided into 3 groups (<45 years, n=8; 45-54, n=9; >54, n=8). Neutrophil characteristics, potential of activation and the ability of NET formation were investigated using flow cytometry. Externalisation of DNA was detected by a DNA release assay. Results: HDN and LDN counts did not differ between age-groups. However, with increasing age we observed a shift in neutrophil subpopulations towards a lower amount of mature LDNs, characterized by their expression of membrane receptors CD62L and CD16. Upon stimulation, neutrophils of older individuals showed significantly higher release of DNA. NET formation was associated with increasing age. HDNs of younger participants increased activation markers (CD66b and CD11b) to a higher extent compared to those of older individuals. Conclusion: Neutrophils and their ability of activation, DNA release and NET formation change with age and this might contribute to the higher risk of infection and thrombosis at advanced age. Furthermore, these results highlight the importance and necessity of age-matching in studies that focus on neutrophil characteristics.

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“…Data on LDN frequency in healthy controls are rarely available and LDN counts vary between reports (25,26). HDN and LDN counts showed no age related differences, however, percentages of mature CD62L high /CD16 high LDNs correlated negatively and percentage of newly released CD16 low LDNs positively with age.…”

Section: Discussionmentioning

confidence: 93%

WITHDRAWN: Age-related changes of neutrophil characteristics, potential of activation, DNA release and NET formation

Krall

Mauracher

Roiß

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Neutrophils are a heterogeneous population of leukocytes, which can be subdivided into high and low density neutrophils (HDNs/LDNs). They are known to fight intruders with different mechanisms, including the release of neutrophil extracellular traps (NETs), which have also been associated with thrombosis. Risks of infection and thrombosis increase with age. Differences in neutrophil subpopulations and functionality have been shown in various disease states, but investigations in healthy subjects and their dependence on age are lacking. The aim of this study was to investigate age-related changes in neutrophils regarding neutrophil subpopulations, their potential of activation, DNA release and NET formation.Methods: Neutrophil subpopulations (HDNs and LDNs) were isolated from 25 healthy individuals subdivided into 3 groups (<45 years, n=8; 45-54, n=9; >54, n=8). Neutrophil characteristics, potential of activation and the ability of NET formation was investigated using flow cytometry. Externalisation of DNA was detected by a DNA release assay.Results: HDN and LDN counts did not differ between age-groups. However, with increasing age we observed a shift in neutrophil subpopulations towards a lower amount of mature LDNs, characterized by their expression of membrane receptors CD62L and CD16. Upon stimulation, neutrophils of older individuals showed significantly higher release of DNA. HDNs of younger participants increased activation markers (CD66b and CD11b) to a higher extent compared to those of older individualsConclusion: Neutrophils and their ability of activation, DNA release and NET formation change with age and this might contribute to the higher risk of infection and thrombosis at advanced age. Furthermore, these results highlight the importance and necessity of age-matching in studies that focus on neutrophil characteristics.

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Low-Density Granulocytes are a novel immunopathological feature in both Multiple Sclerosis and Neuromyelitis optica spectrum disorder

Cited by 9 publications

References 10 publications

Longitudinal analyses reveal immunological misfiring in severe COVID-19

Longitudinal analyses reveal immunological misfiring in severe COVID-19

WITHDRAWN: Age-related changes of neutrophil characteristics, potential of activation, DNA release and NET formation

WITHDRAWN: Age-related changes of neutrophil characteristics, potential of activation, DNA release and NET formation

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