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Halting targeted and collateral damage to red blood cells by the complement system
The complement system is an important defense mechanism against pathogens; however, in certain pathologies, the system also attacks human cells, such as red blood cells (RBCs). In paroxysmal nocturnal hemoglobinuria (PNH), RBCs lack certain complement regulators which sensitize them to complement-me...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243056/ https://www.ncbi.nlm.nih.gov/pubmed/34191092 http://dx.doi.org/10.1007/s00281-021-00859-8 |
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author | Jalink, M. de Boer, E. C. W. Evers, D. Havinga, M. Q. Vos, J. M. I. Zeerleder, S. de Haas, M. Jongerius, I. |
author_facet | Jalink, M. de Boer, E. C. W. Evers, D. Havinga, M. Q. Vos, J. M. I. Zeerleder, S. de Haas, M. Jongerius, I. |
author_sort | Jalink, M. |
collection | PubMed |
description | The complement system is an important defense mechanism against pathogens; however, in certain pathologies, the system also attacks human cells, such as red blood cells (RBCs). In paroxysmal nocturnal hemoglobinuria (PNH), RBCs lack certain complement regulators which sensitize them to complement-mediated lysis, while in autoimmune hemolytic anemia (AIHA), antibodies against RBCs may initiate complement-mediated hemolysis. In recent years, complement inhibition has improved treatment prospects for these patients, with eculizumab now the standard of care for PNH patients. Current complement inhibitors are however not sufficient for all patients, and they come with high costs, patient burden, and increased infection risk. This review gives an overview of the underlying pathophysiology of complement-mediated hemolysis in PNH and AIHA, the role of therapeutic complement inhibition nowadays, and the high number of complement inhibitors currently under investigation, as for almost every complement protein, an inhibitor is being developed. The focus lies with novel therapeutics that inhibit complement activity specifically in the pathway that causes pathology or those that reduce costs or patient burden through novel administration routes. |
format | Online Article Text |
id | pubmed-8243056 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-82430562021-07-01 Halting targeted and collateral damage to red blood cells by the complement system Jalink, M. de Boer, E. C. W. Evers, D. Havinga, M. Q. Vos, J. M. I. Zeerleder, S. de Haas, M. Jongerius, I. Semin Immunopathol Review The complement system is an important defense mechanism against pathogens; however, in certain pathologies, the system also attacks human cells, such as red blood cells (RBCs). In paroxysmal nocturnal hemoglobinuria (PNH), RBCs lack certain complement regulators which sensitize them to complement-mediated lysis, while in autoimmune hemolytic anemia (AIHA), antibodies against RBCs may initiate complement-mediated hemolysis. In recent years, complement inhibition has improved treatment prospects for these patients, with eculizumab now the standard of care for PNH patients. Current complement inhibitors are however not sufficient for all patients, and they come with high costs, patient burden, and increased infection risk. This review gives an overview of the underlying pathophysiology of complement-mediated hemolysis in PNH and AIHA, the role of therapeutic complement inhibition nowadays, and the high number of complement inhibitors currently under investigation, as for almost every complement protein, an inhibitor is being developed. The focus lies with novel therapeutics that inhibit complement activity specifically in the pathway that causes pathology or those that reduce costs or patient burden through novel administration routes. Springer Berlin Heidelberg 2021-06-30 2021 /pmc/articles/PMC8243056/ /pubmed/34191092 http://dx.doi.org/10.1007/s00281-021-00859-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Review Jalink, M. de Boer, E. C. W. Evers, D. Havinga, M. Q. Vos, J. M. I. Zeerleder, S. de Haas, M. Jongerius, I. Halting targeted and collateral damage to red blood cells by the complement system |
title | Halting targeted and collateral damage to red blood cells by the complement system |
title_full | Halting targeted and collateral damage to red blood cells by the complement system |
title_fullStr | Halting targeted and collateral damage to red blood cells by the complement system |
title_full_unstemmed | Halting targeted and collateral damage to red blood cells by the complement system |
title_short | Halting targeted and collateral damage to red blood cells by the complement system |
title_sort | halting targeted and collateral damage to red blood cells by the complement system |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243056/ https://www.ncbi.nlm.nih.gov/pubmed/34191092 http://dx.doi.org/10.1007/s00281-021-00859-8 |
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