Antonia Henes (Düsseldorf / DE), Dr. med. Christopher Nelke (Düsseldorf / DE), Dr. Christina B. Schroeter (Düsseldorf / DE), Dr. Frauke Stascheit (Düsseldorf / DE; Berlin / DE), Dr. Niklas Huntemann (Düsseldorf / DE), Dr. Marc Pawlitzki (Düsseldorf / DE), Allice Willison (Düsseldorf / DE), Saskia Räuber (Düsseldorf / DE), Liesa Regener-Nelke (Düsseldorf / DE), PD Dr. Nico Melzer (Düsseldorf / DE), Kai Stühler (Düsseldorf / DE), Prof. Dr. Andreas Meisel (Berlin / DE), Univ.-Prof. Dr. med. Dr. rer. nat. Sven G. Meuth (Düsseldorf / DE), PD Dr. med. Tobias Ruck (Düsseldorf / DE)
Abstract-Text (inkl. Referenzen)
Introduction:
The complement function is not only limited to the mediation of inflammatory signals but is also intimately linked to cellular processes regulating. Consequently, therapeutic ablation of the terminal complement cascade by eculizumab treatment is likely to impact human biology beyond the control of autoimmunity.
Methods:
We employed an in-depth proteomics and metabolomics approach to dissect the serological profile of anti-acetylcholine receptor-ab MG patients treated with eculizumab compared to patient cohorts treated with azathioprine and treatment naïve patients. Therefore, we included three cohorts with a total of 30 patients (n= 10 per group).
Results:
Analysis of the serum proteome corroborates eculizumab's efficacy for terminal complement ablation with reduction of free C5, which correlated with the treatment response. Distinct immunometabolic pathways were altered in eculizumab-treated patients, including the oxidative stress response, mitogen-activated protein kinase signaling and lipid metabolism with particular emphasis on arachidonic acid signaling. Consistent with this, leukotriene production was reduced in eculizumab-treated patients.
Conclusion:
The current study demonstrates that the eculizumab-induced proteometabolome is a valuable model for understanding the influence of terminal complement ablation on human biology and for exploring potential mechanisms shaping treatment outcomes beyond inhibition of innate immunity.