28
IRUS Total
Downloads
  Altmetric

Biosynthetic homeostasis and resilience of the complement system in health and infectious disease

File Description SizeFormat 
1-s2.0-S2352396419303834-main.pdfPublished version2.37 MBAdobe PDFView/Open
Title: Biosynthetic homeostasis and resilience of the complement system in health and infectious disease
Authors: Willems, E
Alkema, W
Keizer-Garritsen, J
Suppers, A
Van der Flier, M
Philipsen, RHLA
Van den Heuvel, LP
Volokhina, E
Van der Molen, RG
Herberg, JA
Levin, M
Wright, VJ
Ahout, IML
Ferwerda, G
Emonts, M
Boeddha, NP
Rivero-Calle, I
Torres, FM
Wessels, HJCT
De Groot, R
Van Gool, AJ
Gloerich, J
De Jonge, MI
Item Type: Journal Article
Abstract: BACKGROUND: The complement system is a central component of the innate immune system. Constitutive biosynthesis of complement proteins is essential for homeostasis. Dysregulation as a consequence of genetic or environmental cues can lead to inflammatory syndromes or increased susceptibility to infection. However, very little is known about steady state levels in children or its kinetics during infection. METHODS: With a newly developed multiplex mass spectrometry-based method we analyzed the levels of 32 complement proteins in healthy individuals and in a group of pediatric patients infected with bacterial or viral pathogens. FINDINGS: In plasma from young infants we found reduced levels of C4BP, ficolin-3, factor B, classical pathway components C1QA, C1QB, C1QC, C1R, and terminal pathway components C5, C8, C9, as compared to healthy adults; whereas the majority of complement regulating (inhibitory) proteins reach adult levels at very young age. Both viral and bacterial infections in children generally lead to a slight overall increase in complement levels, with some exceptions. The kinetics of complement levels during invasive bacterial infections only showed minor changes, except for a significant increase and decrease of CRP and clusterin, respectively. INTERPRETATION: The combination of lower levels of activating and higher levels of regulating complement proteins, would potentially raise the threshold of activation, which might lead to suppressed complement activation in the first phase of life. There is hardly any measurable complement consumption during bacterial or viral infection. Altogether, expression of the complement proteins appears surprisingly stable, which suggests that the system is continuously replenished. FUND: European Union's Horizon 2020, project PERFORM, grant agreement No. 668303.
Issue Date: 29-Jun-2019
Date of Acceptance: 6-Jun-2019
URI: http://hdl.handle.net/10044/1/71779
DOI: https://doi.org/10.1016/j.ebiom.2019.06.008
ISSN: 2352-3964
Publisher: Elsevier
Start Page: 303
End Page: 313
Journal / Book Title: EBioMedicine
Volume: 45
Copyright Statement: © 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Sponsor/Funder: European Commission
Imperial College London
Funder's Grant Number: Horizon 2020
Keywords: C-reactive protein (CRP)
Clusterin
Complement system
Infectious disease
Multiple reaction monitoring (MRM)
Targeted mass spectrometry
C-reactive protein (CRP)
Clusterin
Complement system
Infectious disease
Multiple reaction monitoring (MRM)
Targeted mass spectrometry
Publication Status: Published
Conference Place: Netherlands
Online Publication Date: 2019-06-29
Appears in Collections:Department of Medicine (up to 2019)