Inter-alpha-trypsin inhibitor heavy chain H3 is a potential biomarker for disease activity in myasthenia gravis

• DOI: 10.1007/s00401-024-02754-6
• Publication Date: 2024-06-18T12:01:56Z
• Authors: Christina B. Schr...; Christopher Nelke; Frauke Stascheit; Niklas Huntemann; Corinna Preusse; Vera Dobelmann; Lukas Theissen; Marc Pawlitzki; Saskia Räuber; Alice Willison; Anna Vogelsang; Adela Della Marina; Hans-Peter Hartung; Nico Melzer; Felix F. Konen; Thomas Skripuletz; Andreas Hentschel; Simone König; Michaela Schweizer; Kai Stühler; Gereon Poschmann; Andreas Roos; Werner Stenzel; Andreas Meisel; Sven G. Meuth; Tobias Ruck
• Keywords: Neuromuscular disease; Neuromuscular transmission

Abstract Myasthenia gravis is a chronic antibody-mediated autoimmune disease disrupting neuromuscular synaptic transmission. Informative biomarkers remain an unmet need to stratify patients with active requiring intensified monitoring and therapy; their identification the primary objective of this study. We applied mass spectrometry-based proteomic serum profiling for biomarker discovery. studied exploration prospective validation cohort consisting 114 140 anti-acetylcholine receptor antibody (AChR-Ab)-positive myasthenia patients, respectively. For downstream analysis, we machine learning approach. Protein expression levels were confirmed by ELISA compared other myasthenic cohorts, in addition myositis neuropathy patients. Anti-AChR-Ab determined radio assay. Immunohistochemistry immunofluorescence intercostal muscle biopsies employed interactome studies inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3). Machine identified ITIH3 as potential reflective activity. Serum correlated activity scores ELISA. Lack correlation between anti-AChR-Ab clinical underlined biomarkers. In subgroup was indicative treatment responses. Immunostaining specimens from these demonstrated localization at endplates but not controls, thus providing structural equivalent our serological findings. Immunoprecipitation subsequent proteomics lead its interaction partners playing crucial roles This study provides data on pathophysiological-relevant gravis. Future are required facilitate translation into practice.