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

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Affiliations

  • 1. Department of Developmental Biology and Cancer Research, The Institute for Medical Research, Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
      Authors
    • Fox-Fisher I 1
    • Piyanzin S 1
    • Ochana BL 1
    • Klochendler A 1
    • Magenheim J 1
    • Peretz A 1
    • Moss J 1
    • Cohen D 1
    • Shemer R 1
    • Dor Y 1
    (10 authors)
  • 2. School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel.
      Authors
    • Loyfer N 2
    • Kaplan T 2
    (2 authors)
  • 3. Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel, and Central Virology Laboratory, Ministry of Health, Chaim Sheba Medical Center, Ramat-Gan, Israel.
      Authors
    • Drori Y 3
    • Friedman N 3
    • Mandelboim M 3
    (3 authors)
  • 4. Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, United States.
      Authors
    • Rothenberg ME 4
    • Caldwell JM 4
    • Rochman M 4
    (3 authors)
  • 5. GRAIL, Menlo Park, United States.
      Authors
    • Jamshidi A 5
    • Cann G 5
    (2 authors)
    • Show all (7)

Elife, 29 Nov 2021, 10:e70520
https://doi.org/10.7554/elife.70520 PMID: 34842142 PMCID: PMC8651286

This article is in the Europe PMC Open access subset. Refer to the copyright information in the article for licensing details.
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This article is based on a previously available preprint.

Abstract 

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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Read article at publisher's site: https://doi.org/10.7554/elife.70520

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    Funding 

    Funders who supported this work.

    Alex U Soyka Pancreatic Cancer Research Fund

      Ernest and Bonnie Beutler Research Program of Excellence in Genomic Medicine

        GRAIL

          Glassman Hebrew University Diabetes Center

            Helmsley Charitable Trust

              Human Islet Research Network (2)

              • Grant ID: HIRN UC4DK104216

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              • Grant ID: HIRN UC4DK116274

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              Israel Science Foundation

                Juvenile Diabetes Research Foundation, International (2)

                • Grant ID: 3-SRA-2014–38

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                • Grant ID: 1-SRA-2019–705

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                NIDDK NIH HHS (2)

                • Grant ID: UC4 DK104216

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                • Grant ID: UC4 DK116274

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                Robert M and Marilyn Sternberg Family Charitable Foundation

                  The DON Foundation

                    Waldholtz/Pakula family

                      Walter and Greta Stiel (2)

                      • Grant ID: Research grant in heart studies

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                      • Grant ID: Chair

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