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
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.