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...

Full description

Bibliographic Details
Main Authors: Ralph Wendt, Justyna Siwy, Tianlin He, Agnieszka Latosinska, Thorsten Wiech, Peter F. Zipfel, Aggeliki Tserga, Antonia Vlahou, Harald Rupprecht, Lorenzo Catanese, Harald Mischak, Joachim Beige
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:Proteomes
Subjects:
Online Access:https://www.mdpi.com/2227-7382/9/4/49
_version_ 1797501114489241600
author Ralph Wendt
Justyna Siwy
Tianlin He
Agnieszka Latosinska
Thorsten Wiech
Peter F. Zipfel
Aggeliki Tserga
Antonia Vlahou
Harald Rupprecht
Lorenzo Catanese
Harald Mischak
Joachim Beige
author_facet Ralph Wendt
Justyna Siwy
Tianlin He
Agnieszka Latosinska
Thorsten Wiech
Peter F. Zipfel
Aggeliki Tserga
Antonia Vlahou
Harald Rupprecht
Lorenzo Catanese
Harald Mischak
Joachim Beige
author_sort Ralph Wendt
collection DOAJ
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.
first_indexed 2024-03-10T03:13:41Z
format Article
id doaj.art-7e8ebd244afd4f9091edf50c0554b3e4
institution Directory Open Access Journal
issn 2227-7382
language English
last_indexed 2024-03-10T03:13:41Z
publishDate 2021-12-01
publisher MDPI AG
record_format Article
series Proteomes
spelling doaj.art-7e8ebd244afd4f9091edf50c0554b3e42023-11-23T10:20:07ZengMDPI AGProteomes2227-73822021-12-01944910.3390/proteomes9040049Molecular Mapping of Urinary Complement Peptides in Kidney DiseasesRalph Wendt0Justyna Siwy1Tianlin He2Agnieszka Latosinska3Thorsten Wiech4Peter F. Zipfel5Aggeliki Tserga6Antonia Vlahou7Harald Rupprecht8Lorenzo Catanese9Harald Mischak10Joachim Beige11Department of Nephrology and Kuratorium for Dialysis and Transplantation (KfH) Renal Unit, Hospital St. Georg, 04129 Leipzig, GermanyMosaiques Diagnostics GmbH, 30659 Hannover, GermanyMosaiques Diagnostics GmbH, 30659 Hannover, GermanyMosaiques Diagnostics GmbH, 30659 Hannover, GermanyNephropathology Section, Institute of Pathology, University Medical Center, 20246 Hamburg, GermanyInstitute of Microbiology, Friedrich-Schiller-University, 07743 Jena, GermanyBiomedical Research Foundation, Academy of Athens, Department of Biotechnology, 11527 Athens, GreeceBiomedical Research Foundation, Academy of Athens, Department of Biotechnology, 11527 Athens, GreeceDepartment of Nephrology, Klinikum Bayreuth GmbH, 95447 Bayreuth, GermanyDepartment of Nephrology, Klinikum Bayreuth GmbH, 95447 Bayreuth, GermanyMosaiques Diagnostics GmbH, 30659 Hannover, GermanyDepartment of Nephrology and Kuratorium for Dialysis and Transplantation (KfH) Renal Unit, Hospital St. Georg, 04129 Leipzig, GermanyDefective 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.https://www.mdpi.com/2227-7382/9/4/49complementpeptideurinebiomarkerkidney diseaseproteomics
spellingShingle Ralph Wendt
Justyna Siwy
Tianlin He
Agnieszka Latosinska
Thorsten Wiech
Peter F. Zipfel
Aggeliki Tserga
Antonia Vlahou
Harald Rupprecht
Lorenzo Catanese
Harald Mischak
Joachim Beige
Molecular Mapping of Urinary Complement Peptides in Kidney Diseases
Proteomes
complement
peptide
urine
biomarker
kidney disease
proteomics
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 complement
peptide
urine
biomarker
kidney disease
proteomics
url https://www.mdpi.com/2227-7382/9/4/49
work_keys_str_mv AT ralphwendt molecularmappingofurinarycomplementpeptidesinkidneydiseases
AT justynasiwy molecularmappingofurinarycomplementpeptidesinkidneydiseases
AT tianlinhe molecularmappingofurinarycomplementpeptidesinkidneydiseases
AT agnieszkalatosinska molecularmappingofurinarycomplementpeptidesinkidneydiseases
AT thorstenwiech molecularmappingofurinarycomplementpeptidesinkidneydiseases
AT peterfzipfel molecularmappingofurinarycomplementpeptidesinkidneydiseases
AT aggelikitserga molecularmappingofurinarycomplementpeptidesinkidneydiseases
AT antoniavlahou molecularmappingofurinarycomplementpeptidesinkidneydiseases
AT haraldrupprecht molecularmappingofurinarycomplementpeptidesinkidneydiseases
AT lorenzocatanese molecularmappingofurinarycomplementpeptidesinkidneydiseases
AT haraldmischak molecularmappingofurinarycomplementpeptidesinkidneydiseases
AT joachimbeige molecularmappingofurinarycomplementpeptidesinkidneydiseases