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

被引：1

作者：

Fox-Fisher, Ilana ^{[1
]}

Piyanzin, Sheina ^{[1
]}

Ochana, Bracha Lea ^{[1
]}

Klochendler, Agnes ^{[1
]}

Magenheim, Judith ^{[1
]}

Peretz, Ayelet ^{[1
]}

Loyfer, Netanel ^{[2
]}

Moss, Joshua ^{[1
]}

Cohen, Daniel ^{[1
]}

Drori, Yaron ^{[3
]}

Friedman, Nehemya ^{[3
]}

Mandelboim, Michal ^{[3
]}

Rothenberg, Marc E. ^{[4
]}

Caldwell, Julie M. ^{[4
]}

Rochman, Mark ^{[4
]}

Jamshidi, Arash ^{[5
]}

Cann, Gordon ^{[5
]}

Lavi, David ^{[6
]}

Kaplan, Tommy ^{[1
,2
]}

Glaser, Benjamin ^{[7
]}

Shemer, Ruth ^{[1
]}

Dor, Yuval ^{[1
]}

机构：

[1] Hebrew Univ Jerusalem Hadassah Hosp & Med Sch, Inst Med Res, Dept Dev Biol & Canc Res, Med Sch, Jerusalem, Israel

[2] Hebrew Univ Jerusalem, Sch Comp Sci & Engn, Jerusalem, Israel

[3] Tel Aviv Univ, Sackler Fac Med, Chaim Sheba Med Ctr, Sch Publ Hlth, Ramat Gan, Israel

[4] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Div Allergy & Immunol, Cincinnati, OH USA

[5] GRAIL, Menlo Pk, CA USA

[6] Hadassah Hebrew Univ, Dept Hematol, Med Ctr, Jerusalem, Israel

[7] Hadassah Hebrew Univ, Endocrinol & Metab Serv, Med Ctr, Jerusalem, Israel

来源：

ELIFE | 2021年 / 10卷

基金：

以色列科学基金会;

关键词：

biomarker; liquid biopsy; DNA methylation; cell-free DNA; vaccination; lymphoma; Human; EOSINOPHILIC ESOPHAGITIS; GENE-EXPRESSION; LIFE-SPAN; INFLUENZA; VACCINATION; LYMPHOMA; AGE; RESPONSES; CONSENSUS; PATTERNS;

D O I：

10.7554/eLife.70520; 10.7554/eLife.70520.sa1; 10.7554/eLife.70520.sa2

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

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.

引用

页数：22

共 58 条

[1] Distinguishing eosinophilic esophagitis in pediatric patients - Clinical, endoscopic, and histologic features of an emerging disorder [J].

Aceves, Seema S. ;

Newbury, Robert O. ;

Dohil, Ranjan ;

Schwimmer, Jeffrey ;

Bastian, John F. .

JOURNAL OF CLINICAL GASTROENTEROLOGY, 2007, 41 (03) :252-256

[2] A clinically meaningful metric of immune age derived from high-dimensional longitudinal monitoring [J].

Alpert, Ayelet ;

Pickman, Yishai ;

Leipold, Michael ;

Rosenberg-Hasson, Yael ;

Ji, Xuhuai ;

Gaujoux, Renaud ;

Rabani, Hadas ;

Starosvetsky, Elina ;

Kveler, Ksenya ;

Schaffert, Steven ;

Furman, David ;

Caspi, Oren ;

Rosenschein, Uri ;

Khatri, Purvesh ;

Dekker, Cornelia L. ;

Maecker, Holden T. ;

Davis, Mark M. ;

Shen-Orr, Shai S. .

NATURE MEDICINE, 2019, 25 (03) :487-+

[3] NORMAL HEMATOLOGICAL VALUES - SEX DIFFERENCE IN NEUTROPHIL COUNT [J].

BAIN, BJ ;

ENGLAND, JM .

BRITISH MEDICAL JOURNAL, 1975, 1 (5953) :306-309

[4] Epigenetic immune cell counting in human blood samples for immunodiagnostics [J].

Baron, Udo ;

Werner, Jeannette ;

Schildknecht, Konstantin ;

Schulze, Janika J. ;

Mulu, Andargaschew ;

Liebert, Uwe-Gerd ;

Sack, Ulrich ;

Speckmann, Carsten ;

Gossen, Manfred ;

Wong, Ronald J. ;

Stevenson, David K. ;

Babel, Nina ;

Schuermann, Dirk ;

Baldinger, Tina ;

Bacchetta, Rosa ;

Gruetzkau, Andreas ;

Borte, Stephan ;

Olek, Sven .

SCIENCE TRANSLATIONAL MEDICINE, 2018, 10 (452)

[5] Role of Imaging in the Staging and Response Assessment of Lymphoma: Consensus of the International Conference on Malignant Lymphomas Imaging Working Group [J].

Barrington, Sally F. ;

Mikhaeel, N. George ;

Kostakoglu, Lale ;

Meignan, Michel ;

Hutchings, Martin ;

Mueeller, Stefan P. ;

Schwartz, Lawrence H. ;

Zucca, Emanuele ;

Fisher, Richard I. ;

Trotman, Judith ;

Hoekstra, Otto S. ;

Hicks, Rodney J. ;

O'Doherty, Michael J. ;

Hustinx, Roland ;

Biggi, Alberto ;

Cheson, Bruce D. .

JOURNAL OF CLINICAL ONCOLOGY, 2014, 32 (27) :3048-+

[6] DNA Sequencing versus Standard Prenatal Aneuploidy Screening [J].

Bianchi, Diana W. ;

Parker, R. Lamar ;

Wentworth, Jeffrey ;

Madankumar, Rajeevi ;

Saffer, Craig ;

Das, Anita F. ;

Craig, Joseph A. ;

Chudova, Darya I. ;

Devers, Patricia L. ;

Jones, Keith W. ;

Oliver, Kelly ;

Rava, Richard P. ;

Sehnert, Amy J. .

NEW ENGLAND JOURNAL OF MEDICINE, 2014, 370 (09) :799-808

[7] Early Patterns of Gene Expression Correlate With the Humoral Immune Response to Influenza Vaccination in Humans [J].

Bucasas, Kristine L. ;

Franco, Luis M. ;

Shaw, Chad A. ;

Bray, Molly S. ;

Wells, Janet M. ;

Nino, Diane ;

Arden, Nancy ;

Quarles, John M. ;

Couch, Robert B. ;

Belmont, John W. .

JOURNAL OF INFECTIOUS DISEASES, 2011, 203 (07) :921-929

[8] The cellular composition of the human immune system is shaped by age and cohabitation [J].

Carr, Edward J. ;

Dooley, James ;

Garcia-Perez, Josselyn E. ;

Lagou, Vasiliki ;

Lee, James C. ;

Wouters, Carine ;

Meyts, Isabelle ;

Goris, An ;

Boeckxstaens, Guy ;

Linterman, Michelle A. ;

Liston, Adrian .

NATURE IMMUNOLOGY, 2016, 17 (04) :461-+

[9] A cell-free DNA metagenomic sequencing assay that integrates the host injury response to infection [J].

Cheng, Alexandre Pellan ;

Burnham, Philip ;

Lee, John Richard ;

Cheng, Matthew Pellan ;

Suthanthiran, Manikkam ;

Dadhania, Darshana ;

De Vlaminck, Iwijn .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2019, 116 (37) :18738-18744

[10]

CONLAN MG, 1991, CANCER, V67, P1389, DOI 10.1002/1097-0142(19910301)67:5<1389::AID-CNCR2820670519>3.0.CO

← 1 2 3 4 5 6 →