Dr. Christina B. Schroeter (Düsseldorf / DE), Dr. med. Christopher Nelke (Düsseldorf / DE), Dr. Frauke Stascheit (Berlin / DE), Dr. Niklas Huntemann (Düsseldorf / DE), Dr. Marc Pawlitzki (Düsseldorf / DE), Saskia Räuber (Düsseldorf / DE), PD Dr. Nico Melzer (Düsseldorf / DE), PD Dr.rer nat Andreas Roos (Essen / DE), Dr. rer. nat. Corinna Preuße (Berlin / DE), Prof. Dr. med Werner Stenzel (Berlin / 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:
Myasthenia gravis (MG) is a chronic antibody (ab)-mediated autoimmune disease disrupting neuromuscular synaptic transmission. Abs against the acetylcholine receptor (AChR) are detected in approximately 85% of patients. Biomarkers reflecting disease activity are lacking for MG.
Material/Methods:
In the current study, we performed mass spectrometry-based proteomic serum profiling of an independent cohort including a total of 114 anti-AChR-ab positive MG patients to dissect their proteome signatures and identify potential biomarkers for MG. We correlated protein levels with clinical parameters using a machine learning (ML) approach. Finally, we validated our findings by IHC.
Results:
Analysis of the serum proteome demonstrated aberrant complement activation in active MG. ML identified inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3) as potential serum biomarker reflective of disease activity. IHC of muscle specimens from these patients proved localization of ITIH3 to the neuromuscular endplates in MG.
Conclusion:
This study provides first data on ITIH3 as a potential biomarker for MG disease activity. We will validate our findings, especially the predictive value of ITIH3, in a second independent cohort of MG patients to substantiate ITIH3 as biomarker. ITIH3 serum levels will be confirmed by ELISAs. Future studies are required to facilitate translation into clinical practice.