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Dimeric IgG complexes from IVIg are incapable of inducing in vitro neutrophil degranulation or complement activation

PURPOSE: Intravenous immunoglobulin (IVIg) products contain various amounts of dimeric IgG complexes. Current insights into the possible biological activities of these dimers remain controversial, and both immunemodulating and immune-activating effects have been reported. Here, we analyzed the putat...

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Autores principales: Kustiawan, Iwan, Derksen, Ninotska I. L., Guhr, Theresa, Kruithof, Simone, Jiskoot, Wim, Vidarsson, Gestur, Rispens, Theo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892932/
https://www.ncbi.nlm.nih.gov/pubmed/29634774
http://dx.doi.org/10.1371/journal.pone.0195729
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author Kustiawan, Iwan
Derksen, Ninotska I. L.
Guhr, Theresa
Kruithof, Simone
Jiskoot, Wim
Vidarsson, Gestur
Rispens, Theo
author_facet Kustiawan, Iwan
Derksen, Ninotska I. L.
Guhr, Theresa
Kruithof, Simone
Jiskoot, Wim
Vidarsson, Gestur
Rispens, Theo
author_sort Kustiawan, Iwan
collection PubMed
description PURPOSE: Intravenous immunoglobulin (IVIg) products contain various amounts of dimeric IgG complexes. Current insights into the possible biological activities of these dimers remain controversial, and both immunemodulating and immune-activating effects have been reported. Here, we analyzed the putative immune-activating effects of dimers isolated from IVIg. METHODS: Dimers isolated from IVIg were purified by high-performance size-exclusion chromatography (HP-SEC) and tested for the ability to induce neutrophil degranulation in vitro. RESULTS: Dimers isolated from IVIg were found to be incapable of inducing in vitro neutrophil degranulation or complement activation, even at concentrations exceeding those expected to be reached upon administration in patients. These results depend on the removal of artefactual activation by using 0.1 micron filtration and the use of poloxamer to prevent adsorption of IgG onto the solid phase. CONCLUSIONS: The data suggest dimeric IgG found in IVIg may bind to Fc-receptors without causing activation.
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spelling pubmed-58929322018-04-20 Dimeric IgG complexes from IVIg are incapable of inducing in vitro neutrophil degranulation or complement activation Kustiawan, Iwan Derksen, Ninotska I. L. Guhr, Theresa Kruithof, Simone Jiskoot, Wim Vidarsson, Gestur Rispens, Theo PLoS One Research Article PURPOSE: Intravenous immunoglobulin (IVIg) products contain various amounts of dimeric IgG complexes. Current insights into the possible biological activities of these dimers remain controversial, and both immunemodulating and immune-activating effects have been reported. Here, we analyzed the putative immune-activating effects of dimers isolated from IVIg. METHODS: Dimers isolated from IVIg were purified by high-performance size-exclusion chromatography (HP-SEC) and tested for the ability to induce neutrophil degranulation in vitro. RESULTS: Dimers isolated from IVIg were found to be incapable of inducing in vitro neutrophil degranulation or complement activation, even at concentrations exceeding those expected to be reached upon administration in patients. These results depend on the removal of artefactual activation by using 0.1 micron filtration and the use of poloxamer to prevent adsorption of IgG onto the solid phase. CONCLUSIONS: The data suggest dimeric IgG found in IVIg may bind to Fc-receptors without causing activation. Public Library of Science 2018-04-10 /pmc/articles/PMC5892932/ /pubmed/29634774 http://dx.doi.org/10.1371/journal.pone.0195729 Text en © 2018 Kustiawan et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Kustiawan, Iwan
Derksen, Ninotska I. L.
Guhr, Theresa
Kruithof, Simone
Jiskoot, Wim
Vidarsson, Gestur
Rispens, Theo
Dimeric IgG complexes from IVIg are incapable of inducing in vitro neutrophil degranulation or complement activation
title Dimeric IgG complexes from IVIg are incapable of inducing in vitro neutrophil degranulation or complement activation
title_full Dimeric IgG complexes from IVIg are incapable of inducing in vitro neutrophil degranulation or complement activation
title_fullStr Dimeric IgG complexes from IVIg are incapable of inducing in vitro neutrophil degranulation or complement activation
title_full_unstemmed Dimeric IgG complexes from IVIg are incapable of inducing in vitro neutrophil degranulation or complement activation
title_short Dimeric IgG complexes from IVIg are incapable of inducing in vitro neutrophil degranulation or complement activation
title_sort dimeric igg complexes from ivig are incapable of inducing in vitro neutrophil degranulation or complement activation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892932/
https://www.ncbi.nlm.nih.gov/pubmed/29634774
http://dx.doi.org/10.1371/journal.pone.0195729
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