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Serum proteomic changes after randomized prolonged erythropoietin treatment and/or endurance training: detection of
Britt Christensen1, Maja Ludvigsen2, Birgitte Nellemann3
1Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark; Medical Research Laboratories, Aarhus University, Aarhus, Denmark; Research Laboratory for Biochemical Pathology, Institute for Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.
Introduction:
Despite implementation of the biological passport to detect erythropoietin abuse, a need for additional biomarkers remains. We used a proteomic approach to identify novel serum biomarkers of prolonged erythropoiesis-stimulating agent (ESA) exposure (Darbepoietin-α) and/or aerobic training.
Trial Design:
Thirty-six healthy young males were randomly assigned to the following groups: Sedentary-placebo (n = 9), Sedentary-ESA (n = 9), Training-placebo (n = 10), or Training-ESA (n = 8). They were treated with placebo/Darbepoietin-α subcutaneously once/week for 10 weeks followed by a 3-week washout period. Training consisted of supervised biking 3/week for 13 weeks at the highest possible intensity. Serum was collected at baseline, week 3 (high dose Darbepoietin-α), week 10 (reduced dose Darbepoietin-α), and after a 3-week washout period.
Methods:
Serum proteins were separated according to charge and molecular mass (2D-gel electrophoresis). The identity of proteins from spots exhibiting altered intensity was determined by mass spectrometry.
Results:
Six protein spots changed in response to Darbepoietin-α treatment. Comparing all 4 experimental groups, two protein spots (serotransferrin and haptoglobin/haptoglobin related protein) showed a significant response to Darbepoietin-α treatment. The haptoglobin/haptoglobin related protein spot showed a significantly lower intensity in all subjects in the training-ESA group during the treatment period and increased during the washout period.
Conclusion:
An isoform of haptoglobin/haptoglobin related protein could be a new anti-doping marker and merits further research.
Trial Registration:
ClinicalTrials.gov NCT01320449.
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