Objectives: Complement deficiencies are difficult to diagnose because of 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.
Methods: 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.
Results: 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.
Conclusion: Our study shows the potential clinical utility of profiling circulating complement
proteins as a comprehensive read-out 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.
Keywords: complement deficiencies; complement system; complementomics; complement‐mediated
diseases; multiplex targeted mass spectrometry; pathway analysis.
Reference
Willems, E., Lorés‐Motta, L., Zanichelli, A., Suffritti, C., van der Flier, M., van der Molen, R. G., ... & de Jonge, M. I. (2020). Quantitative multiplex profiling of the complement system to diagnose complement‐mediated diseases. Clinical & translational immunology, 9(12), e1225.