title: Exercise-induced increases in cell free DNA in human plasma originate predominantly from cells of the haematopoietic lineage.
abstract: The role of cell free DNA (cfDNA) has been intensively discussed under various pathological conditions and after acute bouts of exercise. To date, there is still no conclusive evidence concerning the cellular origin of cfDNA and the entire mechanism leading to elevated cfDNA concentrations in human plasma and serum. Here, we investigated the cellular origin of cfDNA in sex-mismatched haematopoietic stem cell transplantation (HSCT) and liver transplantation (LT) patients by determining the relative proportion of Y-chromosomal to total nuclear cfDNA. Total nuclear cfDNA and Y-chromosomal cfDNA concentrations were determined in blood plasma before and after an incremental exercise test via quantitative real-time PCR (qPCR). Female HSCT patients showed high proportions of Y-chromosomal cfDNA. Both total nuclear and Y-chromosomal cfDNA increased significantly and in a highly correlated fashion due to exercise. In male HSCT patients with female donors less than 10% of the cfDNA was of Y-chromosomal origin at any point in time and even though the total amount of cfDNA increased during exercise, no increases in Y-chromosomal DNA could be detected. The percentage of Y-chromosomal cfDNA in female LT patients with male donors was very low and levels remained unchanged during exercise. This indicates that cells not derived from the bone marrow, in this case transplanted liver cells, represented only a minor fraction of cfDNA in blood plasma and were not released during acute physical exercise. Even though many physiological conditions may be altered in transplant patients versus healthy people, our results strongly suggest that cells from the haematopoietic lineage are the main source of cfDNA released during acute bouts of exercise.
authors.affiliation: Department of Sports Medicine, Disease Prevention and Rehabilitation, Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Suzan
authors.initials: S
authors.lastname: Tug
authors.affiliation: Department of Sports Medicine, Disease Prevention and Rehabilitation, Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Helmig
authors.affiliation: Department of Sports Medicine, Disease Prevention and Rehabilitation, Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Eva Ricarda
authors.initials: ER
authors.lastname: Deichmann
authors.affiliation: Department of Internal Medicine III, Hematology, Oncology and Pneumology, University Medical Center, Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Schmeier-Jürchott
authors.affiliation: Department of Internal Medicine III, Hematology, Oncology and Pneumology, University Medical Center, Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Wagner
authors.affiliation: Department of Internal Medicine I, Transplant Hepatology, University Medical Center, Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Zimmermann
authors.affiliation: Department of Internal Medicine III, Hematology, Oncology and Pneumology, University Medical Center, Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Radsak
authors.affiliation: Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy and Department of Medical, Surgical, and Health Sciences, University of Trieste, Trieste, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Giacca
authors.affiliation: Department of Sports Medicine, Disease Prevention and Rehabilitation, Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Perikles
authors.initials: P
authors.lastname: Simon
mesh_terms: D000328:Adult; D019070:Cell Lineage; D002467:Cell Nucleus / Q000737:chemistry; D041322:Chromosomes, Human, Y / Q000737:chemistry; D004247:DNA / Q000097:blood*; D015444:Exercise; D005080:Exercise Test; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000737:chemistry*; D022781:Hepatocytes / Q000737:chemistry; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009928:Organ Specificity; D010865:Pilot Projects; D010949:Plasma; D012420:Running / Q000502:physiology*; D014019:Tissue Donors; D055815:Young Adult
chemical_list: D004247:DNA
keywords: Y-chromosomal PCR; cell free DNA; exercise; graft rejection; sex-mismatched transplantation