Immunoregulatory properties of cell-free DNA in plasma of celiac disease patients – A pilot study

Brynychova, Iva; Zinková, Alžběta; Hoffmanová, Iva; Korabečná, Marie; Dankova, Pavlina

doi:10.1080/08916934.2019.1608965

Cited by 7 publications

(7 citation statements)

References 39 publications

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“…TNF-α functions as a master regulator of inflammation and ensures tissue homeostasis 47 . We reported the statistically significant differences validated in qPCR experiments earlier on two different occasions-in our study in which plasma samples of healthy volunteers were used for stimulation of THP1 cells 45 and in the report studying the stimulatory capacity of plasma samples obtained from patients with celiac disease 46 . Under the stringent conditions set by us for the evaluation of GeneChip experiments, the TNF-α was not reported as differentially expressed, but its expression was higher in cells treated with TP per our previous results.…”

Section: Discussionmentioning

confidence: 73%

“…Previously, we found elevated expression of another key member of the cytokine network, namely tumor necrosis factor-alpha (TNF-α) in TP treated cells 45,46 . TNF-α functions as a master regulator of inflammation and ensures tissue homeostasis 47 .…”

Section: Discussionmentioning

confidence: 97%

“…We used the THP1 cell line for stimulation experiments. After the recovery of cells from a deep-frozen state, we used the protocol published earlier 45,46 . The cells were stimulated for 3 h in the RPMI 1640 medium (Sigma Aldrich) containing 10% of a plasma sample.…”

Section: Preparation Of Plasma Samples Whole Blood Was Collected Intmentioning

confidence: 99%

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Cell-free DNA in plasma as an essential immune system regulator

Korabečná

Zinková

Brynychova

et al. 2020

Sci Rep

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The cell-free DNA (cfDNA) is always present in plasma, and it is biomarker of growing interest in prenatal diagnostics as well as in oncology and transplantology for therapy efficiency monitoring. But does this cfDNA have a physiological role? Here we show that cfDNA presence and clearance in plasma of healthy individuals plays an indispensable role in immune system regulation. We exposed THP1 cells to healthy individuals’ plasma with (NP) and without (TP) cfDNA. In cells treated with NP, we found elevated expression of genes whose products maintain immune system homeostasis. Exposure of cells to TP triggered an innate immune response (IIR), documented particularly by elevated expression of pro-inflammatory interleukin 8. The results of mass spectrometry showed a higher abundance of proteins associated with IIR activation due to the regulation of complement cascade in cells cultivated with TP. These expression profiles provide evidence that the presence of cfDNA and its clearance in plasma of healthy individuals regulate fundamental mechanisms of the inflammation process and tissue homeostasis. The detailed understanding how neutrophil extracellular traps and their naturally occurring degradation products affect the performance of immune system is of crucial interest for future medical applications.

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 97%

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Cell-free DNA in plasma as an essential immune system regulator

Korabečná

Zinková

Brynychova

et al. 2020

Sci Rep

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“…It should be noted that cfDNA is not only a biomarker for upstream pathophysiological mechanisms but has been also proposed to trigger specific downstream effects. For instance, cfDNA was shown to be an immune system regulator (24) with distinct immunoregulatory properties in healthy and diseased individuals (25). It has also become clear that cfDNA is among the factors contributing to neutrophil extracellular trap (NET) formation.…”

Section: Discussionmentioning

confidence: 99%

Evidence for the utility of cfDNA plasma concentrations to predict disease severity in COVID-19

Hoeter

Neuberger

Fischer

et al. 2021

Preprint

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COVID-19 is a pandemic caused by the highly infective SARS-CoV-2. There is a need for biomarkers not only for overall prognosis but also for predicting the response to treatments and thus for improvements in the clinical management of patients with COVID-19. Circulating cell-free DNA (cfDNA) has emerged as a promising biomarker in the assessment of various disease conditions. The aim of this retrospective and observational pilot study was to examine the potential value of cfDNA plasma concentrations as a correlative biomarker in hospitalized COVID-19 patients. Lithium-Heparin plasma samples were obtained from twenty-one COVID-19 patients during hospitalization in the University Medical Center of Mainz, Germany, and the cfDNA concentrations were determined by quantitative PCR yielding amplicons of long interspersed nuclear elements (LINE-1). cfDNA plasma concentrations of COVID-19 patients ranged between 247.5 and 6346.25 ng/ml and the mean concentrations were 1831 ± 1388 ng/ml (± standard deviation). Correlations were found between cfDNA levels and the occurrence of acute respiratory distress symptom (ARDS), acute kidney injury (AKI), myositis, neurological complications, bacterial superinfection and disease severity as defined by sepsis-related organ failure assessment score (SOFA) score. D-Dimer and C-reactive-protein (CRP), determined by clinical laboratory analysis, showed the highest correlations with cfDNA levels. The results of this observational study suggest that cfDNA plasma concentrations may serve as a predictive biomarker of disease severity in COVID-19. Prospective studies enrolling larger patient cohorts are ongoing to test this hypothesis.

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“…The same needs apply to other autoimmune diseases, featuring very preliminary data. For example, in celiac disease (CD), evidence that plasma cfDNA of patients has different immunoregulatory properties than plasma of healthy controls has been reported [96]; however, there are no differences in the cfDNA concentration between both groups. On the other hand, type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing beta cells of the pancreatic islets of Langerhans, producing chronic inflammation and a progressively severe insulin deficit [97].…”

Section: Circulating Free Dna In Other Autoimmune Disordersmentioning

confidence: 99%

Circulating Free DNA and Its Emerging Role in Autoimmune Diseases

Mondelo‐Macía

Castro‐Santos

Castillo‐García³

et al. 2021

JPM

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Liquid biopsies can be used to analyse tissue-derived information, including cell-free DNA (cfDNA), circulating rare cells, and circulating extracellular vesicles in the blood or other bodily fluids, representing a new way to guide therapeutic decisions in cancer. Among the new challenges of liquid biopsy, we found clinical application in nontumour pathologies, including autoimmune diseases. Since the discovery of the presence of high levels of cfDNA in patients with systemic lupus erythaematosus (SLE) in the 1960s, cfDNA research in autoimmune diseases has mainly focused on the overall quantification of cfDNA and its association with disease activity. However, with technological advancements and the increasing understanding of the role of DNA sensing receptors in inflammation and autoimmunity, interest in cfDNA and autoimmune diseases has not expanded until recently. In this review, we provide an overview of the basic biology of cfDNA in the context of autoimmune diseases as a biomarker of disease activity, progression, and prediction of the treatment response. We discuss and integrate available information about these important aspects.

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Immunoregulatory properties of cell-free DNA in plasma of celiac disease patients – A pilot study

Cited by 7 publications

References 39 publications

Cell-free DNA in plasma as an essential immune system regulator

Cell-free DNA in plasma as an essential immune system regulator

Evidence for the utility of cfDNA plasma concentrations to predict disease severity in COVID-19

Circulating Free DNA and Its Emerging Role in Autoimmune Diseases

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