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Remote immune processes revealed by immune-derived circulating cell-free DNA.

Ilana Fox-Fisher1, Sheina Piyanzin1, Bracha Lea Ochana1

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Summary
This summary is machine-generated.

Cell-free DNA (cfDNA) methylation patterns reveal immune cell dynamics in tissues. This novel biomarker tracks immune responses and predicts vaccine efficacy, offering insights beyond traditional blood counts.

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DNA methylationbiomarkercell-free DNAgeneticsgenomicshumanimmunologyinflammationliquid biopsylymphomavaccination

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Area of Science:

  • Immunology
  • Genomics
  • Biomarker Discovery

Background:

  • Conventional blood cell counts do not fully capture immune activity in remote tissues.
  • Understanding immune cell dynamics is crucial for diagnosing and monitoring various health conditions.

Purpose of the Study:

  • To investigate the utility of immune cell type-specific methylation patterns in circulating cell-free DNA (cfDNA) as a tool for studying human immune cell dynamics.
  • To establish cfDNA as a novel biomarker for monitoring immune responses.

Main Methods:

  • Characterization of cfDNA released from specific immune cell types in healthy individuals (N=242) using cross-sectional and longitudinal analyses.
  • Analysis of cfDNA levels in response to perturbations of immune homeostasis, including influenza vaccination (N=92) and specific diseases (eosinophilic esophagitis N=21, B-cell lymphoma N=27).

Main Results:

  • Immune cfDNA levels exhibited dynamic changes, unlike stable blood cell counts, suggesting cfDNA reflects homeostatic cell survival adjustments.
  • Selective elevation of immune-derived cfDNA was observed during immune perturbations.
  • B-cell-derived cfDNA increased before B-cell count elevation post-vaccination and predicted antibody production efficacy.
  • Elevated eosinophil and B-cell cfDNA were detected in patients with eosinophilic esophagitis and B-cell lymphoma, respectively, even when blood cell counts were normal.

Conclusions:

  • Immune-derived cfDNA serves as a novel biomarker for monitoring immune responses.
  • cfDNA analysis provides insights into immune processes in remote tissues, inaccessible by conventional methods.
  • This approach enhances the understanding of immune dynamics in both physiological and pathological conditions.