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PLoS One. 2014 Oct 21;9(10):e110903. doi: 10.1371/journal.pone.0110903. eCollection 2014.

Recombinant erythropoietin in humans has a prolonged effect on circulating erythropoietin isoform distribution.

Author information

1
Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
2
Clinic of Clinical Physiology, Nuclear Medicine and PET, Centre of Clinical Investigation, Rigshospitalet, Copenhagen, Denmark.
3
Center for Integrative Human Physiology (ZIHP), University of Zurich, Institute of Physiology, Zürich, Switzerland.
4
Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
5
Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark; Department of Neuroanaesthesia, The Neuroscience Centre, Rigshospitalet, Copenhagen, Denmark.

Abstract

The membrane-assisted isoform immunoassay (MAIIA) quantitates erythropoietin (EPO) isoforms as percentages of migrated isoforms (PMI). We evaluated the effect of recombinant human EPO (rhEPO) on the distribution of EPO isoforms in plasma in a randomized, placebo-controlled, double-blinded, cross-over study. 16 healthy subjects received either low-dose Epoetin beta (5000 IU on days 1, 3, 5, 7, 9, 11 and 13); high-dose Epoetin beta (30.000 IU on days 1, 2 and 3 and placebo on days 5, 7, 9, 11 and 13); or placebo on all days. PMI on days 4, 11 and 25 was determined by interaction of N-acetyl glucosamine with the glycosylation dependent desorption of EPO isoforms. At day 25, plasma-EPO in both rhEPO groups had returned to values not different from the placebo group. PMI with placebo, reflecting the endogenous EPO isoforms, averaged 82.5 (10.3) % (mean (SD)). High-dose Epoetin beta decreased PMI on days 4 and 11 to 31.0 (4.2)% (p<0.00001) and 45.2 (7.3)% (p<0.00001). Low-dose Epoetin beta decreased PMI on days 4 and 11 to 46.0 (12.8)% (p<0.00001) and 46.1 (10.4)% (p<0.00001). In both rhEPO groups, PMI on day 25 was still decreased (high-dose Epoetin beta: 72.9 (19.4)% (p=0.029); low-dose Epoetin beta: 73.1 (17.8)% (p=0.039)). In conclusion, Epoetin beta leaves a footprint in the plasma-EPO isoform pattern. MAIIA can detect changes in EPO isoform distribution up til at least three weeks after administration of Epoetin beta even though the total EPO concentration has returned to normal.

PMID:
25335123
PMCID:
PMC4204994
DOI:
10.1371/journal.pone.0110903
[Indexed for MEDLINE]
Free PMC Article

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