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Open Access 01-12-2016 | Research

Differential roles of hypoxia and innate immunity in juvenile and adult dermatomyositis

Authors: Corinna Preuße, Yves Allenbach, Olaf Hoffmann, Hans-Hilmar Goebel, Debora Pehl, Josefine Radke, Alexandra Doeser, Udo Schneider, Rieke H.E. Alten, Tilmann Kallinich, Olivier Benveniste, Arpad von Moers, Benedikt Schoser, Ulrike Schara, Werner Stenzel

Published in: Acta Neuropathologica Communications | Issue 1/2016

Abstract

Dermatomyositis (DM) can occur in both adults and juveniles with considerable clinical differences. The links between immune-mediated mechanisms and vasculopathy with respect to development of perifascicular pathology are incompletely understood. We investigated skeletal muscle from newly diagnosed, treatment-naïve juvenile (jDM) and adult dermatomyositis (aDM) patients focusing on hypoxia-related pathomechanisms, vessel pathology, and immune mechanisms especially in the perifascicular region. Therefore, we assessed the skeletal muscle biopsies from 21 aDM, and 15 jDM patients by immunohistochemistry and electron microscopy. Transcriptional analyses of genes involved in hypoxia, as well as in innate and adaptive immunity were performed by quantitative Polymerase chain reaction (qPCR) of whole tissue cross sections including perifascicular muscle fibers.

Through these analysis, we found that basic features of DM, like perifascicular atrophy and inflammatory infiltrates, were present at similar levels in jDM and aDM patients. However, jDM was characterized by predominantly hypoxia-driven pathology in perifascicular small fibers and by macrophages expressing markers of hypoxia. A more pronounced regional loss of capillaries, but no relevant activation of type-1 Interferon (IFN)-associated pathways was noted. Conversely, in aDM, IFN-related genes were expressed at significantly elevated levels, and Interferon-stimulated gene (ISG)15 was strongly positive in small perifascicular fibers whereas hypoxia-related mechanisms did not play a significant role.

In our study we could provide new molecular data suggesting a conspicuous pathophysiological ‘dichotomy’ between jDM and aDM: In jDM, perifascicular atrophy is tightly linked to hypoxia-related pathology, and poorly to innate immunity. In aDM, perifascicular atrophy is prominently associated with molecules driving innate immunity, while hypoxia-related mechanisms seem to be less relevant.

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Title: Differential roles of hypoxia and innate immunity in juvenile and adult dermatomyositis
Authors: Corinna Preuße
Yves Allenbach
Olaf Hoffmann
Hans-Hilmar Goebel
Debora Pehl
Josefine Radke
Alexandra Doeser
Udo Schneider
Rieke H.E. Alten
Tilmann Kallinich
Olivier Benveniste
Arpad von Moers
Benedikt Schoser
Ulrike Schara
Werner Stenzel
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: Acta Neuropathologica Communications / Issue 1/2016
Electronic ISSN: 2051-5960
DOI: https://doi.org/10.1186/s40478-016-0308-5

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Differential roles of hypoxia and innate immunity in juvenile and adult dermatomyositis

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