Willems, Esther, Lores-Motta, Laura, Zanichelli, Andrea, Suffritti, Chiara, van der Flier, Michiel, van der Molen, Renate G., Langereis, Jeroen D., van Drongelen, Joris, van den Heuvel, Lambert P., Volokhina, Elena, van de Kar, Nicole C. A. J., Keizer-Garritsen, Jenneke, Levin, Michael ORCID: 0000-0003-2767-6919, Herberg, Jethro A., Martinon-Torres, Federico ORCID: 0000-0002-9023-581X, Wessels, Hans J. T. C., de Breuk, Anita, Fauser, Sascha, Hoyng, Carel B., den Hollander, Anneke, I, de Groot, Ronald, van Gool, Alain J., Gloerich, Jolein and de Jonge, Marien, I (2020). Quantitative multiplex profiling of the complement system to diagnose complement-mediated diseases. Clin. Transl. Immunol., 9 (12). HOBOKEN: WILEY. ISSN 2050-0068

Full text not available from this repository.

Abstract

Objectives Complement deficiencies are difficult to diagnose because of the variability of symptoms and the complexity of the diagnostic process. Here, we applied a novel 'complementomics' approach to study the impact of various complement deficiencies on circulating complement levels. Methods Using a quantitative multiplex mass spectrometry assay, we analysed 44 peptides to profile 34 complement proteins simultaneously in 40 healthy controls and 83 individuals with a diagnosed deficiency or a potential pathogenic variant in 14 different complement proteins. Results Apart from confirming near or total absence of the respective protein in plasma of complement-deficient patients, this mass spectrometry-based profiling method led to the identification of additional deficiencies. In many cases, partial depletion of the pathway up- and/or downstream of the absent protein was measured. This was especially found in patients deficient for complement inhibitors, such as angioedema patients with a C1-inhibitor deficiency. The added value of complementomics was shown in three patients with poorly defined complement deficiencies. Conclusion Our study shows the potential clinical utility of profiling circulating complement proteins as a comprehensive read-out of various complement deficiencies. Particularly, our approach provides insight into the intricate interplay between complement proteins due to functional coupling, which contributes to the better understanding of the various disease phenotypes and improvement of care for patients with complement-mediated diseases.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Willems, EstherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lores-Motta, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zanichelli, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Suffritti, ChiaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van der Flier, MichielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van der Molen, Renate G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Langereis, Jeroen D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Drongelen, JorisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van den Heuvel, Lambert P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Volokhina, ElenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van de Kar, Nicole C. A. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Keizer-Garritsen, JennekeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Levin, MichaelUNSPECIFIEDorcid.org/0000-0003-2767-6919UNSPECIFIED
Herberg, Jethro A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martinon-Torres, FedericoUNSPECIFIEDorcid.org/0000-0002-9023-581XUNSPECIFIED
Wessels, Hans J. T. C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Breuk, AnitaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fauser, SaschaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoyng, Carel B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
den Hollander, Anneke, IUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Groot, RonaldUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Gool, Alain J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gloerich, JoleinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Jonge, Marien, IUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-349400
DOI: 10.1002/cti2.1225
Journal or Publication Title: Clin. Transl. Immunol.
Volume: 9
Number: 12
Date: 2020
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 2050-0068
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MANNOSE-BINDING LECTIN; MACULAR DEGENERATION; GENE POLYMORPHISMS; RISK; DYSREGULATION; ASSOCIATION; COMPONENT; DEFICIENCIES; PREVALENCE; ANGIOEDEMAMultiple languages
ImmunologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/34940

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item