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Inter-Individual Variations: A Challenge for the Standardisation of Complement Activation Assays
INTRODUCTION: The role of the human immune system in pathologic responses to chemicals including nanomaterials was identified as a gap in current hazard assessments. However, the complexity of the human immune system as well as interspecies variations make the development of predictive toxicity test...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9930575/ https://www.ncbi.nlm.nih.gov/pubmed/36816333 http://dx.doi.org/10.2147/IJN.S384184 |
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author | Lipsa, Dorelia Ruiz Moreno, Ana Desmet, Cloé Bianchi, Ivana Geiss, Otmar Colpo, Pascal Bremer-Hoffmann, Susanne |
author_facet | Lipsa, Dorelia Ruiz Moreno, Ana Desmet, Cloé Bianchi, Ivana Geiss, Otmar Colpo, Pascal Bremer-Hoffmann, Susanne |
author_sort | Lipsa, Dorelia |
collection | PubMed |
description | INTRODUCTION: The role of the human immune system in pathologic responses to chemicals including nanomaterials was identified as a gap in current hazard assessments. However, the complexity of the human immune system as well as interspecies variations make the development of predictive toxicity tests challenging. In the present study, we have analysed to what extent fluctuations of the complement system of different individuals will have an impact on the standardisation of immunological tests. METHODS: We treated commercially available pooled sera (PS) from healthy males, individual sera from healthy donors and from patients suffering from cancer, immunodeficiency and allergies with small molecules and liposomes. Changes of iC3b protein levels measured in enzyme-linked immunosorbent assays served as biomarker for complement activation. RESULTS: The level of complement activation in PS differed significantly from responses of individual donors (p < 0.01). Only seven out of 32 investigated sera from healthy donors responded similarly to the pooled serum. This variability was even more remarkable when investigating the effect of liposomes on the complement activation in sera from donors with pre-existing pathologies. Neither the 26 sera of donors with allergies nor sera of 16 donors with immunodeficiency responded similar to the PS of healthy donors. Allergy sufferers showed an increase in iC3b levels of 4.16-fold changes when compared to PS treated with liposomes. DISCUSSION: Our studies demonstrate that the use of pooled serum can lead to an over- or under-estimation of immunological response in particular for individuals with pre-existing pathologies. This is of high relevance when developing medical products based on nanomaterials and asks for a review of the current practice to use PS from healthy donors for the prediction of immunological effects of drugs in patients. A better understanding of individual toxicological responses to xenobiotics should be an essential part in safety assessments. |
format | Online Article Text |
id | pubmed-9930575 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-99305752023-02-16 Inter-Individual Variations: A Challenge for the Standardisation of Complement Activation Assays Lipsa, Dorelia Ruiz Moreno, Ana Desmet, Cloé Bianchi, Ivana Geiss, Otmar Colpo, Pascal Bremer-Hoffmann, Susanne Int J Nanomedicine Original Research INTRODUCTION: The role of the human immune system in pathologic responses to chemicals including nanomaterials was identified as a gap in current hazard assessments. However, the complexity of the human immune system as well as interspecies variations make the development of predictive toxicity tests challenging. In the present study, we have analysed to what extent fluctuations of the complement system of different individuals will have an impact on the standardisation of immunological tests. METHODS: We treated commercially available pooled sera (PS) from healthy males, individual sera from healthy donors and from patients suffering from cancer, immunodeficiency and allergies with small molecules and liposomes. Changes of iC3b protein levels measured in enzyme-linked immunosorbent assays served as biomarker for complement activation. RESULTS: The level of complement activation in PS differed significantly from responses of individual donors (p < 0.01). Only seven out of 32 investigated sera from healthy donors responded similarly to the pooled serum. This variability was even more remarkable when investigating the effect of liposomes on the complement activation in sera from donors with pre-existing pathologies. Neither the 26 sera of donors with allergies nor sera of 16 donors with immunodeficiency responded similar to the PS of healthy donors. Allergy sufferers showed an increase in iC3b levels of 4.16-fold changes when compared to PS treated with liposomes. DISCUSSION: Our studies demonstrate that the use of pooled serum can lead to an over- or under-estimation of immunological response in particular for individuals with pre-existing pathologies. This is of high relevance when developing medical products based on nanomaterials and asks for a review of the current practice to use PS from healthy donors for the prediction of immunological effects of drugs in patients. A better understanding of individual toxicological responses to xenobiotics should be an essential part in safety assessments. Dove 2023-02-11 /pmc/articles/PMC9930575/ /pubmed/36816333 http://dx.doi.org/10.2147/IJN.S384184 Text en © 2023 Lipsa et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Lipsa, Dorelia Ruiz Moreno, Ana Desmet, Cloé Bianchi, Ivana Geiss, Otmar Colpo, Pascal Bremer-Hoffmann, Susanne Inter-Individual Variations: A Challenge for the Standardisation of Complement Activation Assays |
title | Inter-Individual Variations: A Challenge for the Standardisation of Complement Activation Assays |
title_full | Inter-Individual Variations: A Challenge for the Standardisation of Complement Activation Assays |
title_fullStr | Inter-Individual Variations: A Challenge for the Standardisation of Complement Activation Assays |
title_full_unstemmed | Inter-Individual Variations: A Challenge for the Standardisation of Complement Activation Assays |
title_short | Inter-Individual Variations: A Challenge for the Standardisation of Complement Activation Assays |
title_sort | inter-individual variations: a challenge for the standardisation of complement activation assays |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9930575/ https://www.ncbi.nlm.nih.gov/pubmed/36816333 http://dx.doi.org/10.2147/IJN.S384184 |
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