title: Recombinant erythropoietin in humans has a prolonged effect on circulating erythropoietin isoform distribution.
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.
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Niels Jacob
authors.initials: NJ
authors.lastname: Aachmann-Andersen
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Just Christensen
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Kristian
authors.initials: K
authors.lastname: Lisbjerg
authors.affiliation: Clinic of Clinical Physiology, Nuclear Medicine and PET, Centre of Clinical Investigation, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Oturai
authors.affiliation: Center for Integrative Human Physiology (ZIHP), University of Zurich, Institute of Physiology, Zürich, Switzerland.
authors.forename: Anne-Kristine
authors.initials: AK
authors.lastname: Meinild-Lundby
authors.affiliation: Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Niels-Henrik
authors.initials: NH
authors.lastname: Holstein-Rathlou
authors.affiliation: Center for Integrative Human Physiology (ZIHP), University of Zurich, Institute of Physiology, Zürich, Switzerland.
authors.forename: Carsten
authors.initials: C
authors.lastname: Lundby
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark; Department of Neuroanaesthesia, The Neuroscience Centre, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Vidiendal Olsen
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004921:Erythropoietin / Q000008:administration & dosage / Q000097:blood* / Q000235:genetics; D006801:Humans; D008297:Male; D020033:Protein Isoforms / Q000097:blood* / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood* / Q000235:genetics
chemical_list: D020033:Protein Isoforms; D011994:Recombinant Proteins; C103998:epoetin beta; D004921:Erythropoietin