4.8 Article

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

Journal

ELIFE
Volume 10, Issue -, Pages -

Publisher

eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.70520

Keywords

biomarker; liquid biopsy; DNA methylation; cell-free DNA; vaccination; lymphoma; Human

Categories

Funding

  1. Juvenile Diabetes Research Foundation [3-SRA-2014-38, 1-SRA-2019-705]
  2. Ernest and Bonnie Beutler Research Program of Excellence in Genomic Medicine
  3. Alex U Soyka Pancreatic Cancer Research Fund
  4. Israel Science Foundation
  5. Waldholtz/Pakula family
  6. Robert M and Marilyn Sternberg Family Charitable Foundation
  7. Helmsley Charitable Trust
  8. GRAIL
  9. DON Foundation
  10. Walter and Greta Stiel Chair
  11. Glassman Hebrew University Diabetes Center
  12. Walter and Greta Stiel Research grant in heart studies

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The immune cell type-specific methylation patterns in circulating cell-free DNA (cfDNA) can be used for studying human immune cell dynamics and provide a novel biomarker for monitoring immune responses to physiological and pathological processes.
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.

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