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Molecular Mapping of Urinary Complement Peptides in Kidney Diseases

Defective complement activation has been associated with various types of kidney disease. This led to the hypothesis that specific urine complement fragments may be associated with kidney disease etiologies, and disease progression may be reflected by changes in these complement fragments. We invest...

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Autores principales: Wendt, Ralph, Siwy, Justyna, He, Tianlin, Latosinska, Agnieszka, Wiech, Thorsten, Zipfel, Peter F., Tserga, Aggeliki, Vlahou, Antonia, Rupprecht, Harald, Catanese, Lorenzo, Mischak, Harald, Beige, Joachim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8709096/
https://www.ncbi.nlm.nih.gov/pubmed/34941814
http://dx.doi.org/10.3390/proteomes9040049
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author Wendt, Ralph
Siwy, Justyna
He, Tianlin
Latosinska, Agnieszka
Wiech, Thorsten
Zipfel, Peter F.
Tserga, Aggeliki
Vlahou, Antonia
Rupprecht, Harald
Catanese, Lorenzo
Mischak, Harald
Beige, Joachim
author_facet Wendt, Ralph
Siwy, Justyna
He, Tianlin
Latosinska, Agnieszka
Wiech, Thorsten
Zipfel, Peter F.
Tserga, Aggeliki
Vlahou, Antonia
Rupprecht, Harald
Catanese, Lorenzo
Mischak, Harald
Beige, Joachim
author_sort Wendt, Ralph
collection PubMed
description Defective complement activation has been associated with various types of kidney disease. This led to the hypothesis that specific urine complement fragments may be associated with kidney disease etiologies, and disease progression may be reflected by changes in these complement fragments. We investigated the occurrence of complement fragments in urine, their association with kidney function and disease etiology in 16,027 subjects, using mass spectrometry based peptidomics data from the Human Urinary Proteome/Peptidome Database. Twenty-three different urinary peptides originating from complement proteins C3, C4 and factor B (CFB) could be identified. Most C3-derived peptides showed inverse association with estimated glomerular filtration rate (eGFR), while the majority of peptides derived from CFB demonstrated positive association with eGFR. Several peptides derived from the complement proteins C3, C4 and CFB were found significantly associated with specific kidney disease etiologies. These peptides may depict disease-specific complement activation and could serve as non-invasive biomarkers to support development of complement interventions through assessing complement activity for patients’ stratification and monitoring of drug impact. Further investigation of these complement peptides may provide additional insight into disease pathophysiology and could possibly guide therapeutic decisions, especially when targeting complement factors.
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spelling pubmed-87090962021-12-25 Molecular Mapping of Urinary Complement Peptides in Kidney Diseases Wendt, Ralph Siwy, Justyna He, Tianlin Latosinska, Agnieszka Wiech, Thorsten Zipfel, Peter F. Tserga, Aggeliki Vlahou, Antonia Rupprecht, Harald Catanese, Lorenzo Mischak, Harald Beige, Joachim Proteomes Article Defective complement activation has been associated with various types of kidney disease. This led to the hypothesis that specific urine complement fragments may be associated with kidney disease etiologies, and disease progression may be reflected by changes in these complement fragments. We investigated the occurrence of complement fragments in urine, their association with kidney function and disease etiology in 16,027 subjects, using mass spectrometry based peptidomics data from the Human Urinary Proteome/Peptidome Database. Twenty-three different urinary peptides originating from complement proteins C3, C4 and factor B (CFB) could be identified. Most C3-derived peptides showed inverse association with estimated glomerular filtration rate (eGFR), while the majority of peptides derived from CFB demonstrated positive association with eGFR. Several peptides derived from the complement proteins C3, C4 and CFB were found significantly associated with specific kidney disease etiologies. These peptides may depict disease-specific complement activation and could serve as non-invasive biomarkers to support development of complement interventions through assessing complement activity for patients’ stratification and monitoring of drug impact. Further investigation of these complement peptides may provide additional insight into disease pathophysiology and could possibly guide therapeutic decisions, especially when targeting complement factors. MDPI 2021-12-13 /pmc/articles/PMC8709096/ /pubmed/34941814 http://dx.doi.org/10.3390/proteomes9040049 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wendt, Ralph
Siwy, Justyna
He, Tianlin
Latosinska, Agnieszka
Wiech, Thorsten
Zipfel, Peter F.
Tserga, Aggeliki
Vlahou, Antonia
Rupprecht, Harald
Catanese, Lorenzo
Mischak, Harald
Beige, Joachim
Molecular Mapping of Urinary Complement Peptides in Kidney Diseases
title Molecular Mapping of Urinary Complement Peptides in Kidney Diseases
title_full Molecular Mapping of Urinary Complement Peptides in Kidney Diseases
title_fullStr Molecular Mapping of Urinary Complement Peptides in Kidney Diseases
title_full_unstemmed Molecular Mapping of Urinary Complement Peptides in Kidney Diseases
title_short Molecular Mapping of Urinary Complement Peptides in Kidney Diseases
title_sort molecular mapping of urinary complement peptides in kidney diseases
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8709096/
https://www.ncbi.nlm.nih.gov/pubmed/34941814
http://dx.doi.org/10.3390/proteomes9040049
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