G.P.64

• Published in: Neuromuscular disorders : NMD 2014-10, Vol.24 (9), p.813-814
• Main Authors: Krause, K, Güttsches, A.K, Maerkens, A, Brady, S, Tegenthoff, M, Holton, J, Marcus, K, Vorgerd, M, Kley, R.A
• Format: Article
• Language: English
• Subjects: Neurology
• ISSN: 0960-8966
• DOI: 10.1016/j.nmd.2014.06.078

Sporadic inclusion body myositis (sIBM) is the most common acquired myopathy in patients >50 years and characterized by both degenerative and autoimmune features. Rimmed vacuoles (RV) are a typical histological finding in sIBM. The aim of our study was to identify proteins that accumulate in RV by using a proteomic approach. Skeletal muscle samples of 18 sIBM patients were included in this study. RV samples and intraindividual control samples (CS; from muscle fibers without vacuolar changes) were collected from 10 μm H&E stained muscle sections by laser microdissection and analyzed by a highly sensitive mass spectrometry approach. A total of 3875 different proteins were identified and 215 of these showed a statistically significant accumulation in RV samples compared to CS. Proteins of the extracellular matrix and of the basal lamina, sarcolemmal proteins and intermediate filaments were the most abundant over-represented proteins in RV. In addition, we found an accumulation of proteins that play a role in protein degradation and of several chaperones including BiP and calreticulin, two proteins that are involved in unfolded protein response and SR stress, and components of a chaperone complex that was not described in the context of sIBM so far. Our proteomic approach also revealed an over-representation of proteins that play a role in inflammatory pathways, e.g. interferon-induced proteins and proteins involved in T-cell activation. In conclusion, our proteomic data provide essential new insights into the composition of rimmed vacuoles in sIBM. The application of a combined laser microdissection and mass spectrometry approach enabled the identification of more than 200 proteins that accumulate in RV areas. The results not only confirm previous findings but expand our knowledge about proteins and pathways that seem to be relevant in pathogenesis of sIBM.