title: Circulating microRNAs as biomarkers for detection of autologous blood transfusion.
abstract: MicroRNAs (miRNAs) are small non-coding RNAs that regulate various biological processes. Cell-free miRNAs measured in blood plasma have emerged as specific and sensitive markers of physiological processes and disease. In this study, we investigated whether circulating miRNAs can serve as biomarkers for the detection of autologous blood transfusion, a major doping technique that is still undetectable. Plasma miRNA levels were analyzed using high-throughput quantitative real-time PCR. Plasma samples were obtained before and at several time points after autologous blood transfusion (blood bag storage time 42 days) in 10 healthy subjects and 10 controls without transfusion. Other serum markers of erythropoiesis were determined in the same samples. Our results revealed a distinct change in the pattern of circulating miRNAs. Ten miRNAs were upregulated in transfusion samples compared with control samples. Among these, miR-30b, miR-30c, and miR-26b increased significantly and showed a 3.9-, 4.0-, and 3.0-fold change, respectively. The origin of these miRNAs was related to pulmonary and liver tissues. Erythropoietin (EPO) concentration decreased after blood reinfusion. A combination of miRNAs and EPO measurement in a mathematical model enhanced the efficiency of autologous transfusion detection through miRNA analysis. Therefore, our results lay the foundation for the development of miRNAs as novel blood-based biomarkers to detect autologous transfusion.
authors.affiliation: Swiss Laboratory for Doping Analyses, University Center of Legal Medicine, Geneva and Lausanne, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland. Nicolas.leuenberger@chuv.ch
authors.forename: Nicolas
authors.initials: N
authors.lastname: Leuenberger
authors.forename: Yorck Olaf
authors.initials: YO
authors.lastname: Schumacher
authors.forename: Sylvain
authors.initials: S
authors.lastname: Pradervand
authors.forename: Thomas
authors.initials: T
authors.lastname: Sander
authors.forename: Martial
authors.initials: M
authors.lastname: Saugy
authors.forename: Torben
authors.initials: T
authors.lastname: Pottgiesser
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001804:Blood Transfusion, Autologous / Q000331:legislation & jurisprudence*; D004300:Doping in Sports; D004921:Erythropoietin / Q000097:blood; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012016:Reference Values; D000685:Serum Amyloid A Protein / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; C554270:EPO protein, human; D035683:MicroRNAs; D000685:Serum Amyloid A Protein; D004921:Erythropoietin