eLife (Nov 2021)
Remote immune processes revealed by immune-derived circulating cell-free DNA
- Ilana Fox-Fisher,
- Sheina Piyanzin,
- Bracha Lea Ochana,
- Agnes Klochendler,
- Judith Magenheim,
- Ayelet Peretz,
- Netanel Loyfer,
- Joshua Moss,
- Daniel Cohen,
- Yaron Drori,
- Nehemya Friedman,
- Michal Mandelboim,
- Marc E Rothenberg,
- Julie M Caldwell,
- Mark Rochman,
- Arash Jamshidi,
- Gordon Cann,
- David Lavi,
- Tommy Kaplan,
- Benjamin Glaser,
- Ruth Shemer,
- Yuval Dor
Affiliations
- Ilana Fox-Fisher
- ORCiD
- Department of Developmental Biology and Cancer Research, The Institute for Medical Research, Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel
- Sheina Piyanzin
- Department of Developmental Biology and Cancer Research, The Institute for Medical Research, Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel
- Bracha Lea Ochana
- Department of Developmental Biology and Cancer Research, The Institute for Medical Research, Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel
- Agnes Klochendler
- Department of Developmental Biology and Cancer Research, The Institute for Medical Research, Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel
- Judith Magenheim
- Department of Developmental Biology and Cancer Research, The Institute for Medical Research, Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel
- Ayelet Peretz
- Department of Developmental Biology and Cancer Research, The Institute for Medical Research, Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel
- Netanel Loyfer
- School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel
- Joshua Moss
- Department of Developmental Biology and Cancer Research, The Institute for Medical Research, Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel
- Daniel Cohen
- Department of Developmental Biology and Cancer Research, The Institute for Medical Research, Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel
- Yaron Drori
- 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
- Nehemya Friedman
- 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
- Michal Mandelboim
- 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
- Marc E Rothenberg
- Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, United States
- Julie M Caldwell
- Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, United States
- Mark Rochman
- ORCiD
- Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, United States
- Arash Jamshidi
- GRAIL, Menlo Park, United States
- Gordon Cann
- GRAIL, Menlo Park, United States
- David Lavi
- Department of Hematology, Hadassah Hebrew University Medical Center, Jerusalem, Israel
- Tommy Kaplan
- ORCiD
- School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel; Department of Developmental Biology and Cancer Research, The Institute for Medical Research, The Hebrew University-Hadassah Medical School, Jerusalem, Israel
- Benjamin Glaser
- Endocrinology and Metabolism Service, Hadassah Hebrew University Medical Center, Jerusalem, Israel
- Ruth Shemer
- Department of Developmental Biology and Cancer Research, The Institute for Medical Research, Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel
- Yuval Dor
- ORCiD
- Department of Developmental Biology and Cancer Research, The Institute for Medical Research, Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel
- DOI
- https://doi.org/10.7554/eLife.70520
- Journal volume & issue
-
Vol. 10
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.
Keywords
