Imperial College London
Dr Victoria Wright

DrVictoriaWright

Faculty of Medicine, Department of Infectious Disease

Research Fellow
 
 
 
//

Contact

 

+44 (0)20 7594 3577v.wright

 
 
//

Location

 

PaediatricsMedical SchoolSt Mary's Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Willems:2019:10.1016/j.ebiom.2019.06.008,
author = {Willems, E and Alkema, W and Keizer-Garritsen, J and Suppers, A and van, der Flier M and Philipsen, RHLA and van, den Heuvel LP and Volokhina, E and van, der Molen RG and Herberg, JA and Levin, M and Wright, VJ and Ahout, IML and Ferwerda, G and Emonts, M and Boeddha, NP and Rivero-Calle, I and Torres, FM and Wessels, HJCT and de, Groot R and van, Gool AJ and Gloerich, J and de, Jonge MI},
doi = {10.1016/j.ebiom.2019.06.008},
journal = {EBioMedicine},
pages = {303--313},
title = {Biosynthetic homeostasis and resilience of the complement system in health and infectious disease},
url = {http://dx.doi.org/10.1016/j.ebiom.2019.06.008},
volume = {45},
year = {2019}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Willems,E
AU  - Alkema,W
AU  - Keizer-Garritsen,J
AU  - Suppers,A
AU  - van,der Flier M
AU  - Philipsen,RHLA
AU  - van,den Heuvel LP
AU  - Volokhina,E
AU  - van,der Molen RG
AU  - Herberg,JA
AU  - Levin,M
AU  - Wright,VJ
AU  - Ahout,IML
AU  - Ferwerda,G
AU  - Emonts,M
AU  - Boeddha,NP
AU  - Rivero-Calle,I
AU  - Torres,FM
AU  - Wessels,HJCT
AU  - de,Groot R
AU  - van,Gool AJ
AU  - Gloerich,J
AU  - de,Jonge MI
DO  - 10.1016/j.ebiom.2019.06.008
EP  - 313
PY  - 2019///
SN  - 2352-3964
SP  - 303
TI  - Biosynthetic homeostasis and resilience of the complement system in health and infectious disease
T2  - EBioMedicine
UR  - http://dx.doi.org/10.1016/j.ebiom.2019.06.008
UR  - https://www.ncbi.nlm.nih.gov/pubmed/31262714
UR  - http://hdl.handle.net/10044/1/71779
VL  - 45
ER  -
Download