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60th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

German Society for Neuropathology and Neuroanatomy

26. - 28.08.2015, Berlin

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Differential roles of hypoxia and innate immune mechanisms in juvenile and adult dermatomyositis

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  • corresponding author presenting/speaker Corinna Preusse - Charité - Universitätsmedizin Berlin, Neuropathology, Berlin, Germany
  • Yves Allenbach - Pitié-Salpêtrière University Hospital, Internal Medicine and Clinical Immunology, Paris, France
  • Hans-Hilmar Goebel - Charité - Universitätsmedizin Berlin, Neuropathology, Berlin, Germany
  • Debora Pehl - Charité - Universitätsmedizin Berlin, Neuropathology, Berlin, Germany
  • Josefine Radke - Charité - Universitätsmedizin Berlin, Neuropathology, Berlin, Germany
  • Olaf Hoffman - St. Josefs Hospital, Neurology, Potsdam, Germany
  • Uwe Schneider - Charité - Universitätsmedizin Berlin, Rheumatology, Berlin, Germany
  • Rieke Alten - Schlossparkklinik, Internal Medicine, Berlin, Germany
  • Mathias Vorgerd - Bergmannsheil, Neurology, Bochum, Germany
  • Arpad von Moers - DRK Klinikum Westend, Pediatrics and Neuropaediatrics, Berlin, Germany
  • Benedikt Schoser - Friedrich-Baur-Institut, Munich, Germany
  • Ulrike Schara - Universitätsklinikum Essen, Neuropediatrics, Essen, Germany
  • Werner Stenzel - Charité - Universitätsmedizin Berlin, Neuropathology, Berlin, Germany; DRK Klinikum Westend, Pediatrics and Neuropaediatrics, Berlin, Germany

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. 60th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN). Berlin, 26.-28.08.2015. Düsseldorf: German Medical Science GMS Publishing House; 2015. Doc15dgnnP39

doi: 10.3205/15dgnn63, urn:nbn:de:0183-15dgnn636

Published: August 25, 2015

© 2015 Preusse et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

Text

Objectives: Dermatomyositis (DM) can occur in both adults and children with considerable clinical differences. The links between immune-mediated mechanisms and vasculopathy with respect to development of perifascicular atrophy are incompletely understood. We investigated skeletal muscle from newly diagnosed juvenile and adult dermatomyositis patients focusing on hypoxia-related pathomechanisms, vessel pathology, and immune mechanisms in the perifascicular region.

Methods: Biopsy specimens from 21 adult-, and 15 juvenile DM patients were assessed by histology and electron microscopy. Laser microdissection and subsequent qPCR transcriptional analyses were performed on perifascicular atrophic muscle fibers. Expression levels of genes involved in hypoxia, innate as well as adaptive immunity were investigated.

Results: Analysis of skeletal muscle derived from juvenile and adult DM patients basically exhibited similar features as perifascicular atrophy and inflammatory infiltrates. However, juvenile patients exhibited predominant HIF1a-driven pathology in atrophic fibers but showed no immunohistochemical reactivity, and only mild expression of IFNa-associated genes, and a more pronounced regional loss of capillaries. Conversely, IFNa-related genes were expressed at significantly elevated levels, and ISG15 was strongly positive in perifascicular atrophic fibers in adult DM patients. In contrast to jDM, hypoxia-related mechanisms did not play a significant role in aDM.

Conclusions: We provide new molecular data with respect to two related pathomechanisms: Hypoxia-related pathology is tightly involved in perifascicular atrophy in jDM, and this is independent of adaptive immunity as illustrated by unchanged IFN-associated gene expression. Conversely, in aDM, perifascicular atrophy is indeed associated with molecules driving innate immunity, while hypoxia-related mechanisms seem to be less relevant.