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

eLife

Benjamin Glaser¹  Agnes Klochendler²  Sheina Piyanzin²  Judith Magenheim²  Joshua Moss²  Ilana Fox-Fisher²  Daniel Cohen²  Bracha Lea Ochana²  Yuval Dor²  Ayelet Peretz²  Michal Mandelboim³  Yaron Drori³  Nehemya Friedman³  David Lavi⁴  Marc E Rothenberg⁵  Mark Rochman⁵  Julie M Caldwell⁵  Ruth Shemer⁶  Gordon Cann⁷  Arash Jamshidi⁷  Netanel Loyfer⁸  Tommy Kaplan⁸ 

[1] Department of Developmental Biology and Cancer Research, The Institute for Medical Research, The Hebrew University-Hadassah Medical School, Jerusalem, Israel;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;

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

DOI  :  10.7554/eLife.70520

来源: DOAJ

【 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】

Unknown