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

eLife

Sheina Piyanzin¹  Bracha Lea Ochana¹  Agnes Klochendler¹  Ayelet Peretz¹  Yuval Dor¹  Ruth Shemer¹  Judith Magenheim¹  Ilana Fox-Fisher¹  Daniel Cohen¹  Joshua Moss¹  Yaron Drori²  Michal Mandelboim²  Nehemya Friedman²  David Lavi³  Julie M Caldwell⁴  Marc E Rothenberg⁴  Mark Rochman⁴  Benjamin Glaser⁵  Arash Jamshidi⁶  Gordon Cann⁶  Netanel Loyfer⁷  Tommy Kaplan⁸ 

[1] Department of Developmental Biology and Cancer Research, The Institute for Medical Research, Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel;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;Department of Hematology, Hadassah Hebrew University Medical Center, Jerusalem, Israel;Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, United States;Endocrinology and Metabolism Service, Hadassah Hebrew University Medical Center, Jerusalem, Israel;GRAIL, Menlo Park, United States;School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel;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;

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

DOI  :  10.7554/eLife.70520

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY