Detection of Stimulated Erythropoiesis by the RNA-Based 5'-Aminolevulinate Synthase 2 Biomarker in Dried Blood Spot Samples
| Autor: | Gemma Reverter-Branchat, Bernard Favrat, Nicolas Leuenberger, Céline Schobinger, Jordi Segura, Olivier Salamin, Martial Saugy, Emeric Gottardo, Tiia Kuuranne, Jean-Daniel Tissot |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine Clinical Biochemistry Pharmacology 01 natural sciences Transcriptome 03 medical and health sciences Blood doping Reticulocyte medicine Humans Erythropoiesis Erythropoietin Doping in Sports business.industry 010401 analytical chemistry Biochemistry (medical) Venous blood Healthy Volunteers 0104 chemical sciences Dried blood spot 030104 developmental biology medicine.anatomical_structure RNA Biomarker (medicine) Female Dried Blood Spot Testing business Biomarkers 5-Aminolevulinate Synthetase medicine.drug |
| Zdroj: | Clinical Chemistry. 65:1563-1571 |
| ISSN: | 1530-8561 0009-9147 |
| DOI: | 10.1373/clinchem.2019.306829 |
| Popis: | BACKGROUNDDespite implementation of the Athlete Biological Passport 10 years ago, blood doping remains difficult to detect. Thus, there is a need for new biomarkers to increase the sensitivity of the adaptive model. Transcriptomic biomarkers originating from immature reticulocytes may be reliable indicators of blood manipulations. Furthermore, the use of dried blood spots (DBSs) for antidoping purposes constitutes a complementary approach to venous blood collection. Here, we developed a method of quantifying the RNA-based 5′-aminolevulinate synthase 2 (ALAS2) biomarker in DBS.MATERIALSThe technical, interindividual, and intraindividual variabilities of the method, and the effects of storage conditions on the production levels of ALAS2 RNA were assessed. The method was used to monitor erythropoiesis stimulated endogenously (blood withdrawal) or exogenously (injection of recombinant human erythropoietin).RESULTSWhen measured over a 7-week period, the intra- and interindividual variabilities of ALAS2 expression in DBS were 12.5%–42.4% and 49%, respectively. Following withdrawal of 1 unit of blood, the ALAS2 RNA in DBS increased significantly for up to 15 days. Variations in the expression level of this biomarker in DBS samples were more marked than those of the conventional hematological parameters, reticulocyte percentage and immature reticulocyte fraction. After exogenous stimulation of erythropoiesis via recombinant human erythropoietin injection, ALAS2 expression in DBS increased by a mean 8-fold.CONCLUSIONSMonitoring of transcriptomic biomarkers in DBS could complement the measurement of hematological parameters in the Athlete Biological Passport and aid the detection of blood manipulations. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|