scholarly journals Elevated levels of circulating cell-free DNA and neutrophil proteins are associated with neonatal sepsis and necrotizing enterocolitis in immature mice, pigs and infants

2017 ◽  
Vol 23 (6) ◽  
pp. 524-536 ◽  
Author(s):  
Duc Ninh Nguyen ◽  
Allan Stensballe ◽  
Jacqueline CY Lai ◽  
Pingping Jiang ◽  
Anders Brunse ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Necrotizing Enterocolitis ◽  
Immune Cell ◽  
Late Onset ◽  
Preterm Neonates ◽  
Cell Free Dna ◽  
Neonatal Mice ◽  
Free Dna ◽  
Associated Proteins ◽  
Circulating Cell Free Dna

Preterm infants are highly susceptible to late-onset sepsis (LOS) and necrotizing enterocolitis (NEC), but disease pathogenesis and specific diagnostic markers are lacking. Circulating cell-free DNA (cfDNA) and immune cell-derived proteins are involved in multiple immune diseases in adults but have not been investigated in preterm neonates. We explored the relation of circulating neutrophil-associated proteins and cfDNA to LOS and/or NEC. Using a clinically relevant preterm pig model of spontaneous LOS and NEC development, we investigated neutrophil-associated proteins and cfDNA in plasma, together with cytokines in gut tissues. The changes in cfDNA levels were further studied in preterm pigs and neonatal mice with induced sepsis, and in preterm infants with or without LOS and/or NEC. Fifteen of 114 preterm pigs spontaneously developed both LOS and NEC, and they showed increased intestinal levels of IL-6 and IL-1β and plasma levels of cfDNA, neutrophil-associated proteins, and proteins involved in platelet-neutrophil interaction during systemic inflammation. The abundance of neutrophil-associated proteins highly correlated with cfDNA levels. Further, Staphylococcus epidermidis challenge of neonatal mice and preterm pigs increased plasma cfDNA levels and bacterial accumulation in the spleen. In infants, plasma cfDNA levels were elevated at LOS diagnosis and 1–6 d before NEC. In conclusion, elevated levels of plasma cfDNA and neutrophil proteins are associated with LOS and NEC diagnosis.

scholarly journals Remote immune processes revealed by immune-derived circulating cell-free DNA

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Ilana Fox-Fisher ◽  
Sheina Piyanzin ◽  
Bracha Lea Ochana ◽  
Agnes Klochendler ◽  
Judith Magenheim ◽  
...  
Keyword(s):  
Blood Cell ◽  
B Cell ◽  
Immune Cell ◽  
B Cell Lymphoma ◽  
Cell Types ◽  
Cell Free Dna ◽  
Cell Counts ◽  
Free Dna ◽  
Blood Cell Counts ◽  
Circulating Cell Free Dna

Blood cell counts often fail to report on immune processes occurring in remote tissues. Here we use immune cell type-specific methylation patterns in circulating cell-free DNA (cfDNA) for studying human immune cell dynamics. We characterized cfDNA released from specific immune cell types in healthy individuals (N=242), cross sectionally and longitudinally. Immune cfDNA levels had no individual steady state as opposed to blood cell counts, suggesting that cfDNA concentration reflects adjustment of cell survival to maintain homeostatic cell numbers. We also observed selective elevation of immune-derived cfDNA upon perturbations of immune homeostasis. Following influenza vaccination (N=92), B-cell-derived cfDNA levels increased prior to elevated B-cell counts and predicted efficacy of antibody production. Patients with Eosinophilic Esophagitis (N=21) and B-cell lymphoma (N=27) showed selective elevation of eosinophil and B-cell cfDNA respectively, which were undetectable by cell counts in blood. Immune-derived cfDNA provides a novel biomarker for monitoring immune responses to physiological and pathological processes that are not accessible using conventional methods.

Immune cell subsets at birth may help to predict risk of late-onset sepsis and necrotizing enterocolitis in preterm infants

2016 ◽  
Vol 93 ◽  
pp. 9-16 ◽  
Author(s):  
Konrad Bochennek ◽  
Esther Fryns ◽  
Boris Wittekindt ◽  
Horst Buxmann ◽  
Andrea Quaiser ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Necrotizing Enterocolitis ◽  
Immune Cell ◽  
Late Onset ◽  
Late Onset Sepsis ◽  
Immune Cell Subsets

scholarly journals Remote immune processes revealed by immune-derived circulating cell-free DNA

2021 ◽  
Author(s):  
Ilana Fox-Fisher ◽  
Sheina Piyanzin ◽  
Agnes Klochendler ◽  
Bracha Lea Ochana ◽  
Judith Magenheim ◽  
...  
Keyword(s):  
Blood Cell ◽  
B Cell ◽  
Immune Cell ◽  
B Cell Lymphoma ◽  
Cell Types ◽  
Cell Free Dna ◽  
Cell Counts ◽  
Free Dna ◽  
Blood Cell Counts ◽  
Circulating Cell Free Dna

Blood cell counts often fail to report on immune processes occurring in remote tissues. Here we use immune cell type-specific methylation patterns in circulating cell-free DNA (cfDNA) for studying human immune cell dynamics. We characterized cfDNA released from specific immune cell types in healthy individuals (N=242), cross sectionally and longitudinally. Immune cfDNA levels had no individual steady state as opposed to blood cell counts, suggesting that cfDNA concentration reflects adjustment of cell survival to maintain homeostatic cell numbers. We also observed selective elevation of immune-derived cfDNA upon perturbations of immune homeostasis. Following influenza vaccination (N=92), B-cell-derived cfDNA levels increased prior to elevated B-cell counts and predicted efficacy of antibody production. Patients with Eosinophilic Esophagitis (N=21) and B-cell lymphoma (N=27) showed selective elevation of eosinophil and B-cell cfDNA respectively, which were undetectable by cell counts in blood. Immune-derived cfDNA provides a novel biomarker for monitoring immune responses to physiological and pathological processes that are not accessible using conventional methods.

scholarly journals 5-Hydroxymethylcytosine Signatures in Circulating Cell-Free DNA as Diagnostic Biomarkers for Late-Onset Alzheimer’s Disease

2021 ◽  
pp. 1-13
Author(s):  
Lei Chen ◽  
Qianqian Shen ◽  
Shunliang Xu ◽  
Hongzhuan Yu ◽  
Shengjie Pei ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Critical Role ◽  
Cell Free Dna ◽  
Free Dna ◽  
Genome Wide ◽  
A Genome ◽  
Normal Controls ◽  
Circulating Cell Free Dna

Background: 5-Hydroxymethylcytosine (5hmC) is an epigenetic DNA modification that is highly abundant in central nervous system. It has been reported that DNA 5hmC dysregulation play a critical role in Alzheimer’s disease (AD) pathology. Changes in 5hmC signatures can be detected in circulating cell-free DNA (cfDNA), which has shown potential as a non-invasive liquid biopsy material. Objective: However, the genome-wide profiling of 5hmC in cfDNA and its potential for the diagnosis of AD has not been reported to date. Methods: We carried out a case-control study and used a genome-wide chemical capture followed by high-throughput sequencing to detect the genome-wide profiles of 5hmC in human cfDNA and identified differentially hydroxymethylated regions (DhMRs) in late-onset AD patients and the control. Results: We discovered significant differences of 5hmC enrichment in gene bodies which were linked to multiple AD pathogenesis-associated signaling pathways in AD patients compared with cognitively normal controls, indicating they can be well distinguished from normal controls by DhMRs in cfDNA. Specially, we identified 7 distinct genes (RABEP1, CPNE4, DNAJC15, REEP3, ROR1, CAMK1D, and RBFOX1) with predicting diagnostic potential based on their significant correlations with MMSE and MoCA scores of subjects. Conclusion: The present results suggest that 5hmC markers derived from plasma cfDNA can served as an effective, minimally invasive biomarkers for clinical auxiliary diagnosis of late-onset AD.

scholarly journals 5-Hydroxymethylcytosine Signatures in Circulating Cell-Free DNA as Diagnostic Biomarkers for Late-Onset Alzheimer’s Disease

2021 ◽  
Author(s):  
Lei Chen ◽  
Shunliang Xu ◽  
Qianqian Shen ◽  
Hongzhuan Yu ◽  
Shengjie Pei ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Cell Free Dna ◽  
Cognitively Normal ◽  
Free Dna ◽  
Genome Wide ◽  
Significant Difference ◽  
Normal Controls ◽  
Circulating Cell Free Dna

Abstract Background: 5-Hydroxymethylcytosine (5hmC) is an epigenetic DNA modification that is highly abundant in nervous system. It has been reported that 5hmC is significant associated with Alzheimer’s disease (AD). Changes in 5hmC signatures can be detected in circulating cell-free DNA (cfDNA), which has shown potential as a non-invasive liquid biopsy material. However, there is no research about genome-wide profiling of 5hmC in cfDNA and its potential for the diagnosis of AD to date. Methods: We carried out a case-control study and used a highly sensitive and selective high-throughput sequencing of chemical labels to detect the genome-wide profiles of 5hmC in human cfDNA and identified differentially hydroxymethylated regions (DhMRs) in AD patients and the control. Results: We detected a significant difference of 5hmC enrichment in gene bodies which were linked to multiple AD pathogenesis-associated signaling pathways in AD patients compared with cognitively normal controls. AD patients can be well distinguished from cognitively normal controls by differentially hydroxymethylated regions (DhMRs) in cfDNA. Specially, we found 7 distinct genes (RABEP1, CPNE4, DNAJC15, REEP3, ROR1, CAMK1D, and RBFOX1) had prediction diagnostic potential based on their significant correlations with MMSE and MoCA scores. Conclusions: The present results suggest that 5hmC markers derived from plasma cfDNA can be served as an effective, minimally invasive biomarkers for clinical auxiliary diagnosis of late-onset AD. Trial registration: Chinese Clinical Trial Registry, ChiCTR2100042537, registered 13 January 2021-retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=120582.

304-OR: 5-Hydroxymethylcytosines in Circulating Cell-Free DNA Reveal Diabetic Nephropathy

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 304-OR
Author(s):  
CHANG ZENG ◽  
YING YANG ◽  
ZHOU ZHANG ◽  
CHUAN HE ◽  
WEI ZHANG ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Cell Free Dna ◽  
Free Dna ◽  
Circulating Cell Free Dna
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