Targeted MRM assay Complement System in Health and Infectious Disease
Willems E, Alkema W, Keizer-Garritsen J, Suppers A, van der Flier M, Philipsen RH, van den Heuvel LP, Volokhina E, van der Molen RG, Herberg JA, Levin M. Biosynthetic homeostasis and resilience of the complement system in health and infectious disease. EBioMedicine. 2019 Jun 29.
- Organism: Homo sapiens
- Instrument: Xevo TQ-S
targeted mass spectrometry, multiple reaction monitoring (MRM), complement system, infectious disease, C-reactive protein (CRP), clusterin
Lab head: Jolein Gloerich
Submitter: Esther Willems
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.
With a new multiplex mass spectrometry-based method we analyzed 32 complement protein levels in healthy individuals and in a group of pediatric patients infected with bacterial or viral pathogens.
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.
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.
Comparison of a healthy control group to a patient group
Created on 6/16/19, 3:57 PM