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May 2018; 5 (3) ArticleOpen Access

Architectural B-cell organization in skeletal muscle identifies subtypes of dermatomyositis

Josefine Radke, Randi Koll, Corinna Preuße, Debora Pehl, Kremena Todorova, Constanze Schönemann, Yves Allenbach, Eleonora Aronica, Marianne de Visser, Frank L. Heppner, Joachim Weis, Soroush Doostkam, Thierry Maisonobe, Olivier Benveniste, Hans-Hilmar Goebel, Werner Stenzel
First published March 6, 2018, DOI: https://doi.org/10.1212/NXI.0000000000000451
Josefine Radke
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Randi Koll
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Corinna Preuße
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Debora Pehl
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Kremena Todorova
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Constanze Schönemann
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Yves Allenbach
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Eleonora Aronica
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Marianne de Visser
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Frank L. Heppner
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Joachim Weis
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Soroush Doostkam
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Thierry Maisonobe
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Olivier Benveniste
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Hans-Hilmar Goebel
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Werner Stenzel
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Architectural B-cell organization in skeletal muscle identifies subtypes of dermatomyositis
Josefine Radke, Randi Koll, Corinna Preuße, Debora Pehl, Kremena Todorova, Constanze Schönemann, Yves Allenbach, Eleonora Aronica, Marianne de Visser, Frank L. Heppner, Joachim Weis, Soroush Doostkam, Thierry Maisonobe, Olivier Benveniste, Hans-Hilmar Goebel, Werner Stenzel
Neurol Neuroimmunol Neuroinflamm May 2018, 5 (3) e451; DOI: 10.1212/NXI.0000000000000451

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Abstract

Objective To study the B-cell content, organization, and existence of distinct B-cell subpopulations in relation to the expression of type 1 interferon signature related genes in dermatomyositis (DM).

Methods Evaluation of skeletal muscle biopsies from patients with adult DM (aDM) and juvenile DM (jDM) by histology, immunohistochemistry, electron microscopy, and quantitative reverse-transcription PCR.

Results We defined 3 aDM subgroups—classic (containing occasional B cells without clusters), B-cell–rich, and follicle-like aDM—further elucidating IM B-lymphocyte maturation and immunity. The quantity of B cells and formation of ectopic lymphoid structures in a subset of patients with aDM were associated with a specific profile of cytokines and chemokines involved in lymphoid neogenesis. Levels of type 1 interferon signature related gene expression paralleled B-cell content and architectural organization and link B-cell immunity to the interferon type I signature.

Conclusion These data corroborate the important role of B cells in DM, highlighting the direct link between humoral mechanisms as key players in B-cell immunity and the role of type I interferon–related immunity.

Glossary

aDM=
adult dermatomyositis;
CK=
creatine kinase;
DM=
dermatomyositis;
ELS=
ectopic lymphoid structure;
EM=
electron microscopy;
ENMC=
European Neuromuscular Centre;
HEV=
high endothelial venule;
IFN=
interferon;
jDM=
juvenile dermatomyositis;
MHC=
major histocompatibility complex;
mRNA=
messenger RNA;
MxA=
myxovirus resistance gene A;
qPCR=
quantitative PCR;
RIN=
RNA integrity number;
TRI=
tubuloreticular inclusion;
VAS=
visual analog scale

Footnotes

  • Funding information and disclosures are provided at the end of the article. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/NN.

  • Received December 1, 2017.
  • Accepted in final form February 2, 2018.
  • Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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