Radboud University Medical Center Translational Metabolic Lab - Targeted MRM assay Complement System for Complement deficiencies

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Panorama_patient_cys-method.sky.zip2020-11-09 20:32:4836499828883
Panorama_patient_mox-method.sky.zip2020-11-09 07:41:4636499828883
Panorama_controls_cys-method.sky.zip2020-11-07 14:53:1836499828840
Panorama_controls_mox-method.sky.zip2020-11-07 14:53:1836499828840
Targeted MRM assay Complement System for Complement deficiencies

  • Organism: Homo sapiens
  • Instrument: Xevo TQ-S
  • SpikeIn: Yes
  • Keywords: complement system, complementomics, complement deficiencies, complement-mediated diseases, multiplex targeted mass spectrometry, pathway analysis
  • Lab head: Jolein Gloerich
Abstract
Complement deficiencies are difficult to diagnose due to 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. 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. 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. Our study shows the potential clinical utility of profiling circulating complement proteins as a comprehensive read-oud 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.
Experiment Description
Comparison of various complement deficiencies to a control group
Sample Description
Plasma
Created on 11/7/20, 2:54 PM