Dermatomyositis with or without anti-melanoma differentiation-associated gene 5 antibodies common interferon signature but distinct NOS2 expression

Yves Allenbach; Gaëlle Leroux; Xavier Suárez-Calvet; Corinna Preusse; Eduard Gallardo; Baptiste Hervier; Aude Rigolet; Miguel Hie; Debora Pehl; Nicolas Limal; Peter Hufnagl; Norman Zerbe; Alain Meyer; Jessie Aouizerate; Yurdagul Uzunhan; Thierry Maisonobe; Hans Hilmar Goebel; Olivier Benveniste; Werner Stenzel; Arnaud Hot; Aurélie Grados; Nicolas Schleinitz; Laure Gallet; Nathalie Streichenberger; Philippe Petiot; Eric Hachulla; David Launay; Hervé Devilliers; Mohamed Hamidou; Divy Cornec; Boris Bienvenu; Vincent Langlois; Hervé Levesque; Aurélien Delluc; Laurent Drouot; Jean Luc Charuel; Fabienne Jouen; Norma Romero; Odile Dubourg; Sarah Leonard-Louis; Anthony Behin; Pascal Laforet; Tania Stojkovic; Bruno Eymard; Nathalie Costedoat-Chalumeau; Emmanuelle Campana-Salort; Anne Tournadre; Lucile Musset; Brigitte Bader-Meunier; Isabelle Kone-Paut; Jean Sibilia; Laurent Servais; Olivier Fain; Claire Larroche; Elizabeth Diot; Benjamin Terrier; Raphaël De Paz; Antoine Dossier; Dominique Menard; Chafika Morati; Marielle Roux; Xavier Ferrer; Jeremy Martinet; Sophie Besnard; Rémi Bellance; Patrice Cacoub; David Saadoun; Laurent Arnaud; Bernard Grosbois; Serge Herson; Olivier Boyer

doi:10.1016/j.ajpath.2015.11.010

Dermatomyositis with or without anti-melanoma differentiation-associated gene 5 antibodies common interferon signature but distinct NOS2 expression

Yves Allenbach, Gaëlle Leroux, Xavier Suárez-Calvet, Corinna Preusse, Eduard Gallardo, Baptiste Hervier, Aude Rigolet, Miguel Hie, Debora Pehl, Nicolas Limal, Peter Hufnagl, Norman Zerbe, Alain Meyer, Jessie Aouizerate, Yurdagul Uzunhan, Thierry Maisonobe, Hans Hilmar Goebel, Olivier Benveniste, Werner Stenzel, Arnaud HotAurélie Grados, Nicolas Schleinitz, Laure Gallet, Nathalie Streichenberger, Philippe Petiot, Eric Hachulla, David Launay, Hervé Devilliers, Mohamed Hamidou, Divy Cornec, Boris Bienvenu, Vincent Langlois, Hervé Levesque, Aurélien Delluc, Laurent Drouot, Jean Luc Charuel, Fabienne Jouen, Norma Romero, Odile Dubourg, Sarah Leonard-Louis, Anthony Behin, Pascal Laforet, Tania Stojkovic, Bruno Eymard, Nathalie Costedoat-Chalumeau, Emmanuelle Campana-Salort, Anne Tournadre, Lucile Musset, Brigitte Bader-Meunier, Isabelle Kone-Paut, Jean Sibilia, Laurent Servais, Olivier Fain, Claire Larroche, Elizabeth Diot, Benjamin Terrier, Raphaël De Paz, Antoine Dossier, Dominique Menard, Chafika Morati, Marielle Roux, Xavier Ferrer, Jeremy Martinet, Sophie Besnard, Rémi Bellance, Patrice Cacoub, David Saadoun, Laurent Arnaud, Bernard Grosbois, Serge Herson, Olivier Boyer

Research output: Contribution to journal › Article › Research › peer-review

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Abstract

© Copyright 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. The anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody is specifically associated with dermatomyositis (DM). Nevertheless, anti-MDA5+-patients experience characteristic symptoms distinct from classic DM, including severe signs of extramuscular involvement; however, the clinical signs of myopathy are mild or even absent. The morphological and immunological features are not yet described in adulthood. Data concerning the pathophysiology of anti-MDA5 DM are sparse; however, the importance of the interferon (IFN) type I pathway involved in DM has been shown. Our aim was to define morphological alterations of the skeletal muscle and the intrinsic immune response of anti-MDA5-positive DM patients. Immunohistological and RT-PCR analysis of muscle biopsy specimens from anti-MDA5 and classic DM were compared. Those with anti-MDA5 DM did not present the classic features of perifascicular fiber atrophy and major histocompatibility complex class I expression. They did not show significant signs of capillary loss; tubuloreticular formations were observed less frequently. Inflammation was focal, clustering around single vessels but significantly less intense. Expression of IFN-stimulated genes was up-regulated in anti-MDA5 DM; however, the IFN score was significantly lower. Characteristic features were observed in anti-MDA5 DM and not in classic DM patients. Only anti-MDA5 DM showed numerous nitric oxide synthase 2-positive muscle fibers with sarcoplasmic colocalization of markers of regeneration and cell stress. Anti-MDA5-positive patients demonstrate a morphological pattern distinct from classic DM.

Original language	English
Pages (from-to)	691-700
Journal	American Journal of Pathology
Volume	186
Issue number	3
DOIs	https://doi.org/10.1016/j.ajpath.2015.11.010
Publication status	Published - 1 Mar 2016

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Allenbach, Y., Leroux, G., Suárez-Calvet, X., Preusse, C., Gallardo, E., Hervier, B., Rigolet, A., Hie, M., Pehl, D., Limal, N., Hufnagl, P., Zerbe, N., Meyer, A., Aouizerate, J., Uzunhan, Y., Maisonobe, T., Goebel, H. H., Benveniste, O., Stenzel, W., ... Boyer, O. (2016). Dermatomyositis with or without anti-melanoma differentiation-associated gene 5 antibodies common interferon signature but distinct NOS2 expression. American Journal of Pathology, 186(3), 691-700. https://doi.org/10.1016/j.ajpath.2015.11.010

Allenbach, Yves ; Leroux, Gaëlle ; Suárez-Calvet, Xavier ; Preusse, Corinna ; Gallardo, Eduard ; Hervier, Baptiste ; Rigolet, Aude ; Hie, Miguel ; Pehl, Debora ; Limal, Nicolas ; Hufnagl, Peter ; Zerbe, Norman ; Meyer, Alain ; Aouizerate, Jessie ; Uzunhan, Yurdagul ; Maisonobe, Thierry ; Goebel, Hans Hilmar ; Benveniste, Olivier ; Stenzel, Werner ; Hot, Arnaud ; Grados, Aurélie ; Schleinitz, Nicolas ; Gallet, Laure ; Streichenberger, Nathalie ; Petiot, Philippe ; Hachulla, Eric ; Launay, David ; Devilliers, Hervé ; Hamidou, Mohamed ; Cornec, Divy ; Bienvenu, Boris ; Langlois, Vincent ; Levesque, Hervé ; Delluc, Aurélien ; Drouot, Laurent ; Charuel, Jean Luc ; Jouen, Fabienne ; Romero, Norma ; Dubourg, Odile ; Leonard-Louis, Sarah ; Behin, Anthony ; Laforet, Pascal ; Stojkovic, Tania ; Eymard, Bruno ; Costedoat-Chalumeau, Nathalie ; Campana-Salort, Emmanuelle ; Tournadre, Anne ; Musset, Lucile ; Bader-Meunier, Brigitte ; Kone-Paut, Isabelle ; Sibilia, Jean ; Servais, Laurent ; Fain, Olivier ; Larroche, Claire ; Diot, Elizabeth ; Terrier, Benjamin ; De Paz, Raphaël ; Dossier, Antoine ; Menard, Dominique ; Morati, Chafika ; Roux, Marielle ; Ferrer, Xavier ; Martinet, Jeremy ; Besnard, Sophie ; Bellance, Rémi ; Cacoub, Patrice ; Saadoun, David ; Arnaud, Laurent ; Grosbois, Bernard ; Herson, Serge ; Boyer, Olivier. / Dermatomyositis with or without anti-melanoma differentiation-associated gene 5 antibodies common interferon signature but distinct NOS2 expression. In: American Journal of Pathology. 2016 ; Vol. 186, No. 3. pp. 691-700.

@article{ad09318dbb6f42608ab72f332d6c0460,

title = "Dermatomyositis with or without anti-melanoma differentiation-associated gene 5 antibodies common interferon signature but distinct NOS2 expression",

abstract = "{\textcopyright} Copyright 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. The anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody is specifically associated with dermatomyositis (DM). Nevertheless, anti-MDA5+-patients experience characteristic symptoms distinct from classic DM, including severe signs of extramuscular involvement; however, the clinical signs of myopathy are mild or even absent. The morphological and immunological features are not yet described in adulthood. Data concerning the pathophysiology of anti-MDA5 DM are sparse; however, the importance of the interferon (IFN) type I pathway involved in DM has been shown. Our aim was to define morphological alterations of the skeletal muscle and the intrinsic immune response of anti-MDA5-positive DM patients. Immunohistological and RT-PCR analysis of muscle biopsy specimens from anti-MDA5 and classic DM were compared. Those with anti-MDA5 DM did not present the classic features of perifascicular fiber atrophy and major histocompatibility complex class I expression. They did not show significant signs of capillary loss; tubuloreticular formations were observed less frequently. Inflammation was focal, clustering around single vessels but significantly less intense. Expression of IFN-stimulated genes was up-regulated in anti-MDA5 DM; however, the IFN score was significantly lower. Characteristic features were observed in anti-MDA5 DM and not in classic DM patients. Only anti-MDA5 DM showed numerous nitric oxide synthase 2-positive muscle fibers with sarcoplasmic colocalization of markers of regeneration and cell stress. Anti-MDA5-positive patients demonstrate a morphological pattern distinct from classic DM.",

author = "Yves Allenbach and Ga{\"e}lle Leroux and Xavier Su{\'a}rez-Calvet and Corinna Preusse and Eduard Gallardo and Baptiste Hervier and Aude Rigolet and Miguel Hie and Debora Pehl and Nicolas Limal and Peter Hufnagl and Norman Zerbe and Alain Meyer and Jessie Aouizerate and Yurdagul Uzunhan and Thierry Maisonobe and Goebel, {Hans Hilmar} and Olivier Benveniste and Werner Stenzel and Arnaud Hot and Aur{\'e}lie Grados and Nicolas Schleinitz and Laure Gallet and Nathalie Streichenberger and Philippe Petiot and Eric Hachulla and David Launay and Herv{\'e} Devilliers and Mohamed Hamidou and Divy Cornec and Boris Bienvenu and Vincent Langlois and Herv{\'e} Levesque and Aur{\'e}lien Delluc and Laurent Drouot and Charuel, {Jean Luc} and Fabienne Jouen and Norma Romero and Odile Dubourg and Sarah Leonard-Louis and Anthony Behin and Pascal Laforet and Tania Stojkovic and Bruno Eymard and Nathalie Costedoat-Chalumeau and Emmanuelle Campana-Salort and Anne Tournadre and Lucile Musset and Brigitte Bader-Meunier and Isabelle Kone-Paut and Jean Sibilia and Laurent Servais and Olivier Fain and Claire Larroche and Elizabeth Diot and Benjamin Terrier and {De Paz}, Rapha{\"e}l and Antoine Dossier and Dominique Menard and Chafika Morati and Marielle Roux and Xavier Ferrer and Jeremy Martinet and Sophie Besnard and R{\'e}mi Bellance and Patrice Cacoub and David Saadoun and Laurent Arnaud and Bernard Grosbois and Serge Herson and Olivier Boyer",

year = "2016",

month = mar,

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doi = "10.1016/j.ajpath.2015.11.010",

language = "English",

volume = "186",

pages = "691--700",

journal = "American Journal of Pathology",

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Allenbach, Y, Leroux, G, Suárez-Calvet, X, Preusse, C, Gallardo, E, Hervier, B, Rigolet, A, Hie, M, Pehl, D, Limal, N, Hufnagl, P, Zerbe, N, Meyer, A, Aouizerate, J, Uzunhan, Y, Maisonobe, T, Goebel, HH, Benveniste, O, Stenzel, W, Hot, A, Grados, A, Schleinitz, N, Gallet, L, Streichenberger, N, Petiot, P, Hachulla, E, Launay, D, Devilliers, H, Hamidou, M, Cornec, D, Bienvenu, B, Langlois, V, Levesque, H, Delluc, A, Drouot, L, Charuel, JL, Jouen, F, Romero, N, Dubourg, O, Leonard-Louis, S, Behin, A, Laforet, P, Stojkovic, T, Eymard, B, Costedoat-Chalumeau, N, Campana-Salort, E, Tournadre, A, Musset, L, Bader-Meunier, B, Kone-Paut, I, Sibilia, J, Servais, L, Fain, O, Larroche, C, Diot, E, Terrier, B, De Paz, R, Dossier, A, Menard, D, Morati, C, Roux, M, Ferrer, X, Martinet, J, Besnard, S, Bellance, R, Cacoub, P, Saadoun, D, Arnaud, L, Grosbois, B, Herson, S & Boyer, O 2016, 'Dermatomyositis with or without anti-melanoma differentiation-associated gene 5 antibodies common interferon signature but distinct NOS2 expression', American Journal of Pathology, vol. 186, no. 3, pp. 691-700. https://doi.org/10.1016/j.ajpath.2015.11.010

Dermatomyositis with or without anti-melanoma differentiation-associated gene 5 antibodies common interferon signature but distinct NOS2 expression. / Allenbach, Yves; Leroux, Gaëlle; Suárez-Calvet, Xavier; Preusse, Corinna; Gallardo, Eduard; Hervier, Baptiste; Rigolet, Aude; Hie, Miguel; Pehl, Debora; Limal, Nicolas; Hufnagl, Peter; Zerbe, Norman; Meyer, Alain; Aouizerate, Jessie; Uzunhan, Yurdagul; Maisonobe, Thierry; Goebel, Hans Hilmar; Benveniste, Olivier; Stenzel, Werner; Hot, Arnaud; Grados, Aurélie; Schleinitz, Nicolas; Gallet, Laure; Streichenberger, Nathalie; Petiot, Philippe; Hachulla, Eric; Launay, David; Devilliers, Hervé; Hamidou, Mohamed; Cornec, Divy; Bienvenu, Boris; Langlois, Vincent; Levesque, Hervé; Delluc, Aurélien; Drouot, Laurent; Charuel, Jean Luc; Jouen, Fabienne; Romero, Norma; Dubourg, Odile; Leonard-Louis, Sarah; Behin, Anthony; Laforet, Pascal; Stojkovic, Tania; Eymard, Bruno; Costedoat-Chalumeau, Nathalie; Campana-Salort, Emmanuelle; Tournadre, Anne; Musset, Lucile; Bader-Meunier, Brigitte; Kone-Paut, Isabelle; Sibilia, Jean; Servais, Laurent; Fain, Olivier; Larroche, Claire; Diot, Elizabeth; Terrier, Benjamin; De Paz, Raphaël; Dossier, Antoine; Menard, Dominique; Morati, Chafika; Roux, Marielle; Ferrer, Xavier; Martinet, Jeremy; Besnard, Sophie; Bellance, Rémi; Cacoub, Patrice; Saadoun, David; Arnaud, Laurent; Grosbois, Bernard; Herson, Serge; Boyer, Olivier.

In: American Journal of Pathology, Vol. 186, No. 3, 01.03.2016, p. 691-700.

Research output: Contribution to journal › Article › Research › peer-review

TY - JOUR

T1 - Dermatomyositis with or without anti-melanoma differentiation-associated gene 5 antibodies common interferon signature but distinct NOS2 expression

AU - Allenbach, Yves

AU - Leroux, Gaëlle

AU - Suárez-Calvet, Xavier

AU - Preusse, Corinna

AU - Gallardo, Eduard

AU - Hervier, Baptiste

AU - Rigolet, Aude

AU - Hie, Miguel

AU - Pehl, Debora

AU - Limal, Nicolas

AU - Hufnagl, Peter

AU - Zerbe, Norman

AU - Meyer, Alain

AU - Aouizerate, Jessie

AU - Uzunhan, Yurdagul

AU - Maisonobe, Thierry

AU - Goebel, Hans Hilmar

AU - Benveniste, Olivier

AU - Stenzel, Werner

AU - Hot, Arnaud

AU - Grados, Aurélie

AU - Schleinitz, Nicolas

AU - Gallet, Laure

AU - Streichenberger, Nathalie

AU - Petiot, Philippe

AU - Hachulla, Eric

AU - Launay, David

AU - Devilliers, Hervé

AU - Hamidou, Mohamed

AU - Cornec, Divy

AU - Bienvenu, Boris

AU - Langlois, Vincent

AU - Levesque, Hervé

AU - Delluc, Aurélien

AU - Drouot, Laurent

AU - Charuel, Jean Luc

AU - Jouen, Fabienne

AU - Romero, Norma

AU - Dubourg, Odile

AU - Leonard-Louis, Sarah

AU - Behin, Anthony

AU - Laforet, Pascal

AU - Stojkovic, Tania

AU - Eymard, Bruno

AU - Costedoat-Chalumeau, Nathalie

AU - Campana-Salort, Emmanuelle

AU - Tournadre, Anne

AU - Musset, Lucile

AU - Bader-Meunier, Brigitte

AU - Kone-Paut, Isabelle

AU - Sibilia, Jean

AU - Servais, Laurent

AU - Fain, Olivier

AU - Larroche, Claire

AU - Diot, Elizabeth

AU - Terrier, Benjamin

AU - De Paz, Raphaël

AU - Dossier, Antoine

AU - Menard, Dominique

AU - Morati, Chafika

AU - Roux, Marielle

AU - Ferrer, Xavier

AU - Martinet, Jeremy

AU - Besnard, Sophie

AU - Bellance, Rémi

AU - Cacoub, Patrice

AU - Saadoun, David

AU - Arnaud, Laurent

AU - Grosbois, Bernard

AU - Herson, Serge

AU - Boyer, Olivier

PY - 2016/3/1

Y1 - 2016/3/1

N2 - © Copyright 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. The anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody is specifically associated with dermatomyositis (DM). Nevertheless, anti-MDA5+-patients experience characteristic symptoms distinct from classic DM, including severe signs of extramuscular involvement; however, the clinical signs of myopathy are mild or even absent. The morphological and immunological features are not yet described in adulthood. Data concerning the pathophysiology of anti-MDA5 DM are sparse; however, the importance of the interferon (IFN) type I pathway involved in DM has been shown. Our aim was to define morphological alterations of the skeletal muscle and the intrinsic immune response of anti-MDA5-positive DM patients. Immunohistological and RT-PCR analysis of muscle biopsy specimens from anti-MDA5 and classic DM were compared. Those with anti-MDA5 DM did not present the classic features of perifascicular fiber atrophy and major histocompatibility complex class I expression. They did not show significant signs of capillary loss; tubuloreticular formations were observed less frequently. Inflammation was focal, clustering around single vessels but significantly less intense. Expression of IFN-stimulated genes was up-regulated in anti-MDA5 DM; however, the IFN score was significantly lower. Characteristic features were observed in anti-MDA5 DM and not in classic DM patients. Only anti-MDA5 DM showed numerous nitric oxide synthase 2-positive muscle fibers with sarcoplasmic colocalization of markers of regeneration and cell stress. Anti-MDA5-positive patients demonstrate a morphological pattern distinct from classic DM.

AB - © Copyright 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. The anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody is specifically associated with dermatomyositis (DM). Nevertheless, anti-MDA5+-patients experience characteristic symptoms distinct from classic DM, including severe signs of extramuscular involvement; however, the clinical signs of myopathy are mild or even absent. The morphological and immunological features are not yet described in adulthood. Data concerning the pathophysiology of anti-MDA5 DM are sparse; however, the importance of the interferon (IFN) type I pathway involved in DM has been shown. Our aim was to define morphological alterations of the skeletal muscle and the intrinsic immune response of anti-MDA5-positive DM patients. Immunohistological and RT-PCR analysis of muscle biopsy specimens from anti-MDA5 and classic DM were compared. Those with anti-MDA5 DM did not present the classic features of perifascicular fiber atrophy and major histocompatibility complex class I expression. They did not show significant signs of capillary loss; tubuloreticular formations were observed less frequently. Inflammation was focal, clustering around single vessels but significantly less intense. Expression of IFN-stimulated genes was up-regulated in anti-MDA5 DM; however, the IFN score was significantly lower. Characteristic features were observed in anti-MDA5 DM and not in classic DM patients. Only anti-MDA5 DM showed numerous nitric oxide synthase 2-positive muscle fibers with sarcoplasmic colocalization of markers of regeneration and cell stress. Anti-MDA5-positive patients demonstrate a morphological pattern distinct from classic DM.

U2 - 10.1016/j.ajpath.2015.11.010

DO - 10.1016/j.ajpath.2015.11.010

M3 - Article

VL - 186

SP - 691

EP - 700

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 3

ER -

Dermatomyositis with or without anti-melanoma differentiation-associated gene 5 antibodies common interferon signature but distinct NOS2 expression

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