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Published on: September 9, 2020
Remote immune processes revealed by immune-derived circulating cell-free DNA
Ilana Fox-Fisher1, Sheina Piyanzin1, Bracha Lea Ochana1
1Department of Developmental Biology and Cancer Research, The Institute for Medical Research, Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Insights
Cell-free DNA (cfDNA) methylation patterns reveal immune cell dynamics in tissues. This novel biomarker tracks immune responses and predicts vaccine efficacy, offering insights beyond traditional blood counts.
Area of Science:
- Immunology
- Genomics
- Biomarker Discovery
Background:
- Conventional blood cell counts do not fully capture immune activity in remote tissues.
- Understanding immune cell dynamics is crucial for diagnosing and monitoring various health conditions.
Purpose of the Study:
- To investigate the utility of immune cell type-specific methylation patterns in circulating cell-free DNA (cfDNA) as a tool for studying human immune cell dynamics.
- To establish cfDNA as a novel biomarker for monitoring immune responses.
Main Methods:
- Characterization of cfDNA released from specific immune cell types in healthy individuals (N=242) using cross-sectional and longitudinal analyses.
- Analysis of cfDNA levels in response to perturbations of immune homeostasis, including influenza vaccination (N=92) and specific diseases (eosinophilic esophagitis N=21, B-cell lymphoma N=27).
Main Results:
- Immune cfDNA levels exhibited dynamic changes, unlike stable blood cell counts, suggesting cfDNA reflects homeostatic cell survival adjustments.
- Selective elevation of immune-derived cfDNA was observed during immune perturbations.
- B-cell-derived cfDNA increased before B-cell count elevation post-vaccination and predicted antibody production efficacy.
- Elevated eosinophil and B-cell cfDNA were detected in patients with eosinophilic esophagitis and B-cell lymphoma, respectively, even when blood cell counts were normal.
Conclusions:
- Immune-derived cfDNA serves as a novel biomarker for monitoring immune responses.
- cfDNA analysis provides insights into immune processes in remote tissues, inaccessible by conventional methods.
- This approach enhances the understanding of immune dynamics in both physiological and pathological conditions.
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.
