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

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

来源:bioRxiv_logobioRxiv
英文摘要

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.

Shemer Ruth、Cann Gordon、Kaplan Tommy、Fox-Fisher Ilana、Ochana Bracha-Lea、Klochendler Agnes、Peretz Ayelet、Cohen Daniel、Drori Yaron、Friedman Nehemya、Rochman Mark、Rothenberg Marc E.、Lavi David、Jamshidi Arash、Glaser Benjamin、Dor Yuval、Piyanzin Sheina、Loyfer Netanel、Mandelboim Michal、Caldwell Julie M.、Magenheim Judith、Moss Joshua

Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical SchoolGRAIL, Menlo ParkSchool of Computer Science and Engineering, The Hebrew University of JerusalemDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical SchoolDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical SchoolDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical SchoolDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical SchoolDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical SchoolDepartment 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 CenterDepartment 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 CenterDivision of Allergy and Immunology, Department of Pediatrics, Cincinnati Children?ˉs Hospital Medical Center, University of CincinnatiDivision of Allergy and Immunology, Department of Pediatrics, Cincinnati Children?ˉs Hospital Medical Center, University of CincinnatiDepartment of Hematology, Hadassah Hebrew University Medical CenterGRAIL, Menlo ParkEndocrinology and Metabolism Service, Hadassah-Hebrew University Medical CenterDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical SchoolDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical SchoolSchool of Computer Science and Engineering, The Hebrew University of JerusalemDepartment 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 CenterDivision of Allergy and Immunology, Department of Pediatrics, Cincinnati Children?ˉs Hospital Medical Center, University of CincinnatiDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical SchoolDepartment of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School

10.1101/2021.09.13.460029

基础医学生物科学研究方法、生物科学研究技术分子生物学

Shemer Ruth,Cann Gordon,Kaplan Tommy,Fox-Fisher Ilana,Ochana Bracha-Lea,Klochendler Agnes,Peretz Ayelet,Cohen Daniel,Drori Yaron,Friedman Nehemya,Rochman Mark,Rothenberg Marc E.,Lavi David,Jamshidi Arash,Glaser Benjamin,Dor Yuval,Piyanzin Sheina,Loyfer Netanel,Mandelboim Michal,Caldwell Julie M.,Magenheim Judith,Moss Joshua.Remote immune processes revealed by immune-derived circulating cell-free DNA[EB/OL].(2025-03-28)[2025-07-01].https://www.biorxiv.org/content/10.1101/2021.09.13.460029.点此复制

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