Quantitative proteome profiling provides evidence of an activation of the complement cascade in ATTR amyloidosis
Christian Treitz, Juliane Gottwald, Eva Gericke, Péter Urbán, Rolf Rüdiger Meliß, Hans-Detlef Axmann, Frank T. Siebert, Karsten Becker, Andreas Tholey, Christoph Röcken
Abstract
Amyloidosis is a disease group caused by pathological aggregation and deposition of peptides in diverse tissue sites. Apart from the fibril protein, amyloid deposits frequently enclose non-fibrillar constituents. In this study, carpal tunnel tissue sections with ATTR amyloid were analysed by quantitative mass spectrometry-based proteomics. Following manual dissection, tissue samples of equal size and with heterogeneous amyloid load were dissected and forwarded to bottom-up proteome analysis and label-free protein profiling. The amyloid-associated proteins showed significant correlations of label-free intensity profiles. A comprehensive list of 83 proteins specifically enriched in amyloid deposits was discovered. In addition to well-known signature proteins (e.g. apolipoprotein E, apolipoprotein A-IV, and vitronectin), 22 members of the complement system, including all seven components of the membrane attack complex could be associated to the disease. These data lend support to the hypothesis that the complement system is activated in ATTR amyloidosis.