Recombinant erythropoietin in humans has a prolonged effect on circulating erythropoietin isoform distribution.
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-ove...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4204994?pdf=render |
| _version_ | 1818581669324521472 |
|---|---|
| author | Niels Jacob Aachmann-Andersen Søren Just Christensen Kristian Lisbjerg Peter Oturai Anne-Kristine Meinild-Lundby Niels-Henrik Holstein-Rathlou Carsten Lundby Niels Vidiendal Olsen |
| author_facet | Niels Jacob Aachmann-Andersen Søren Just Christensen Kristian Lisbjerg Peter Oturai Anne-Kristine Meinild-Lundby Niels-Henrik Holstein-Rathlou Carsten Lundby Niels Vidiendal Olsen |
| author_sort | Niels Jacob Aachmann-Andersen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-16T07:37:10Z |
| format | Article |
| id | doaj.art-2f48a99020b844bea74a8f5593682748 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-16T07:37:10Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-2f48a99020b844bea74a8f55936827482022-12-21T22:39:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01910e11090310.1371/journal.pone.0110903Recombinant erythropoietin in humans has a prolonged effect on circulating erythropoietin isoform distribution.Niels Jacob Aachmann-AndersenSøren Just ChristensenKristian LisbjergPeter OturaiAnne-Kristine Meinild-LundbyNiels-Henrik Holstein-RathlouCarsten LundbyNiels Vidiendal OlsenThe 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.http://europepmc.org/articles/PMC4204994?pdf=render |
| spellingShingle | Niels Jacob Aachmann-Andersen Søren Just Christensen Kristian Lisbjerg Peter Oturai Anne-Kristine Meinild-Lundby Niels-Henrik Holstein-Rathlou Carsten Lundby Niels Vidiendal Olsen Recombinant erythropoietin in humans has a prolonged effect on circulating erythropoietin isoform distribution. PLoS ONE |
| title | Recombinant erythropoietin in humans has a prolonged effect on circulating erythropoietin isoform distribution. |
| title_full | Recombinant erythropoietin in humans has a prolonged effect on circulating erythropoietin isoform distribution. |
| title_fullStr | Recombinant erythropoietin in humans has a prolonged effect on circulating erythropoietin isoform distribution. |
| title_full_unstemmed | Recombinant erythropoietin in humans has a prolonged effect on circulating erythropoietin isoform distribution. |
| title_short | Recombinant erythropoietin in humans has a prolonged effect on circulating erythropoietin isoform distribution. |
| title_sort | recombinant erythropoietin in humans has a prolonged effect on circulating erythropoietin isoform distribution |
| url | http://europepmc.org/articles/PMC4204994?pdf=render |
| work_keys_str_mv | AT nielsjacobaachmannandersen recombinanterythropoietininhumanshasaprolongedeffectoncirculatingerythropoietinisoformdistribution AT sørenjustchristensen recombinanterythropoietininhumanshasaprolongedeffectoncirculatingerythropoietinisoformdistribution AT kristianlisbjerg recombinanterythropoietininhumanshasaprolongedeffectoncirculatingerythropoietinisoformdistribution AT peteroturai recombinanterythropoietininhumanshasaprolongedeffectoncirculatingerythropoietinisoformdistribution AT annekristinemeinildlundby recombinanterythropoietininhumanshasaprolongedeffectoncirculatingerythropoietinisoformdistribution AT nielshenrikholsteinrathlou recombinanterythropoietininhumanshasaprolongedeffectoncirculatingerythropoietinisoformdistribution AT carstenlundby recombinanterythropoietininhumanshasaprolongedeffectoncirculatingerythropoietinisoformdistribution AT nielsvidiendalolsen recombinanterythropoietininhumanshasaprolongedeffectoncirculatingerythropoietinisoformdistribution |