Muscle Expression of Type I and Type II Interferons Is Increased in Juvenile Dermatomyositis and Related to Clinical and Histological Features

Gian Marco Moneta, Denise Pires Marafon, Emiliano Marasco, Silvia Rosina, Margherita Verardo, Chiara Fiorillo, Carlo Minetti, Luisa Bracci-Laudiero, Angelo Ravelli, Fabrizio De Benedetti, Rebecca Nicolai

Research output: Contribution to journalArticle

Abstract

OBJECTIVES: Our aim was to evaluate expression of type I interferon (IFNα/β)- and type II IFN (IFNγ)-inducible genes in muscle biopsies of JDM patients and to correlate their expression levels with histological and clinical features.

METHODS: Expression levels of IFN-inducible genes and pro-inflammatory cytokines were assessed by quantitative PCR in muscle biopsies of JDM patients (n = 39), Duchenne muscular dystrophy (DMD) patients (n = 24) and healthy controls (HCs) (n = 4). Histological and immunofluorescence studies were performed on muscle biopsy sections. For each JDM patient charts were reviewed to record clinical features at time of sampling and long-term outcomes.

RESULTS: Expression levels of IFNα/β-inducible genes (type I IFN score), IFNγ, IFNγ-inducible genes (type II IFN score), and TNFα were significantly higher in untreated JDM patients compared to DMD patients and HCs. Both type I and type II IFN scores were correlated with typical histopathological features of JDM muscle biopsies, such as infiltration of CD3+ and CD68+ cells and perifascicular atrophy. JDM patients with high type I IFN score, high type II IFN score and high TNFα expression levels showed more severe disease activity at biopsy. JDM patients with high type II IFN score at biopsy reached clinically inactive disease significantly later than patients with low type II IFN score.

CONCLUSION: The increased expression of IFN-inducible genes in muscle of JDM patients and their association with histological and clinical features further support the pathogenic role in JDM for both type I and type II IFNs. This article is protected by copyright. All rights reserved.

Original languageEnglish
JournalArthritis and Rheumatology
DOIs
Publication statusE-pub ahead of print - Dec 15 2018

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Interferon-gamma
Muscles
Biopsy
Duchenne Muscular Dystrophy
Genes
Juvenile dermatomyositis
Interferon Type I
Interferons
Atrophy
Fluorescent Antibody Technique
Cytokines
Polymerase Chain Reaction

Cite this

@article{d0a3953b21bc4c178b15d030abb057a3,
title = "Muscle Expression of Type I and Type II Interferons Is Increased in Juvenile Dermatomyositis and Related to Clinical and Histological Features",
abstract = "OBJECTIVES: Our aim was to evaluate expression of type I interferon (IFNα/β)- and type II IFN (IFNγ)-inducible genes in muscle biopsies of JDM patients and to correlate their expression levels with histological and clinical features.METHODS: Expression levels of IFN-inducible genes and pro-inflammatory cytokines were assessed by quantitative PCR in muscle biopsies of JDM patients (n = 39), Duchenne muscular dystrophy (DMD) patients (n = 24) and healthy controls (HCs) (n = 4). Histological and immunofluorescence studies were performed on muscle biopsy sections. For each JDM patient charts were reviewed to record clinical features at time of sampling and long-term outcomes.RESULTS: Expression levels of IFNα/β-inducible genes (type I IFN score), IFNγ, IFNγ-inducible genes (type II IFN score), and TNFα were significantly higher in untreated JDM patients compared to DMD patients and HCs. Both type I and type II IFN scores were correlated with typical histopathological features of JDM muscle biopsies, such as infiltration of CD3+ and CD68+ cells and perifascicular atrophy. JDM patients with high type I IFN score, high type II IFN score and high TNFα expression levels showed more severe disease activity at biopsy. JDM patients with high type II IFN score at biopsy reached clinically inactive disease significantly later than patients with low type II IFN score.CONCLUSION: The increased expression of IFN-inducible genes in muscle of JDM patients and their association with histological and clinical features further support the pathogenic role in JDM for both type I and type II IFNs. This article is protected by copyright. All rights reserved.",
author = "Moneta, {Gian Marco} and {Pires Marafon}, Denise and Emiliano Marasco and Silvia Rosina and Margherita Verardo and Chiara Fiorillo and Carlo Minetti and Luisa Bracci-Laudiero and Angelo Ravelli and {De Benedetti}, Fabrizio and Rebecca Nicolai",
note = "This article is protected by copyright. All rights reserved.",
year = "2018",
month = "12",
day = "15",
doi = "10.1002/art.40800",
language = "English",
journal = "Arthritis and Rheumatology",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",

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TY - JOUR

T1 - Muscle Expression of Type I and Type II Interferons Is Increased in Juvenile Dermatomyositis and Related to Clinical and Histological Features

AU - Moneta, Gian Marco

AU - Pires Marafon, Denise

AU - Marasco, Emiliano

AU - Rosina, Silvia

AU - Verardo, Margherita

AU - Fiorillo, Chiara

AU - Minetti, Carlo

AU - Bracci-Laudiero, Luisa

AU - Ravelli, Angelo

AU - De Benedetti, Fabrizio

AU - Nicolai, Rebecca

N1 - This article is protected by copyright. All rights reserved.

PY - 2018/12/15

Y1 - 2018/12/15

N2 - OBJECTIVES: Our aim was to evaluate expression of type I interferon (IFNα/β)- and type II IFN (IFNγ)-inducible genes in muscle biopsies of JDM patients and to correlate their expression levels with histological and clinical features.METHODS: Expression levels of IFN-inducible genes and pro-inflammatory cytokines were assessed by quantitative PCR in muscle biopsies of JDM patients (n = 39), Duchenne muscular dystrophy (DMD) patients (n = 24) and healthy controls (HCs) (n = 4). Histological and immunofluorescence studies were performed on muscle biopsy sections. For each JDM patient charts were reviewed to record clinical features at time of sampling and long-term outcomes.RESULTS: Expression levels of IFNα/β-inducible genes (type I IFN score), IFNγ, IFNγ-inducible genes (type II IFN score), and TNFα were significantly higher in untreated JDM patients compared to DMD patients and HCs. Both type I and type II IFN scores were correlated with typical histopathological features of JDM muscle biopsies, such as infiltration of CD3+ and CD68+ cells and perifascicular atrophy. JDM patients with high type I IFN score, high type II IFN score and high TNFα expression levels showed more severe disease activity at biopsy. JDM patients with high type II IFN score at biopsy reached clinically inactive disease significantly later than patients with low type II IFN score.CONCLUSION: The increased expression of IFN-inducible genes in muscle of JDM patients and their association with histological and clinical features further support the pathogenic role in JDM for both type I and type II IFNs. This article is protected by copyright. All rights reserved.

AB - OBJECTIVES: Our aim was to evaluate expression of type I interferon (IFNα/β)- and type II IFN (IFNγ)-inducible genes in muscle biopsies of JDM patients and to correlate their expression levels with histological and clinical features.METHODS: Expression levels of IFN-inducible genes and pro-inflammatory cytokines were assessed by quantitative PCR in muscle biopsies of JDM patients (n = 39), Duchenne muscular dystrophy (DMD) patients (n = 24) and healthy controls (HCs) (n = 4). Histological and immunofluorescence studies were performed on muscle biopsy sections. For each JDM patient charts were reviewed to record clinical features at time of sampling and long-term outcomes.RESULTS: Expression levels of IFNα/β-inducible genes (type I IFN score), IFNγ, IFNγ-inducible genes (type II IFN score), and TNFα were significantly higher in untreated JDM patients compared to DMD patients and HCs. Both type I and type II IFN scores were correlated with typical histopathological features of JDM muscle biopsies, such as infiltration of CD3+ and CD68+ cells and perifascicular atrophy. JDM patients with high type I IFN score, high type II IFN score and high TNFα expression levels showed more severe disease activity at biopsy. JDM patients with high type II IFN score at biopsy reached clinically inactive disease significantly later than patients with low type II IFN score.CONCLUSION: The increased expression of IFN-inducible genes in muscle of JDM patients and their association with histological and clinical features further support the pathogenic role in JDM for both type I and type II IFNs. This article is protected by copyright. All rights reserved.

U2 - 10.1002/art.40800

DO - 10.1002/art.40800

M3 - Article

C2 - 30552836

JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

SN - 2326-5191

ER -