Biosynthetic homeostasis and resilience of the complement system in health and infectious disease
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Published version
Author(s)
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.
Date Issued
2019-06-29
Date Acceptance
2019-06-06
Citation
EBioMedicine, 2019, 45, pp.303-313
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
European Commission
Imperial College London
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/31262714
PII: S2352-3964(19)30383-4
Grant Number
Horizon 2020
Subjects
C-reactive protein (CRP)
Clusterin
Complement system
Infectious disease
Multiple reaction monitoring (MRM)
Targeted mass spectrometry
Publication Status
Published
Coverage Spatial
Netherlands
Date Publish Online
2019-06-29