Premium
Muscle Expression of Type I and Type II Interferons Is Increased in Juvenile Dermatomyositis and Related to Clinical and Histologic Features
Author(s) -
Moneta Gian Marco,
Pires Marafon Denise,
Marasco Emiliano,
Rosina Silvia,
Verardo Margherita,
Fiorillo Chiara,
Minetti Carlo,
BracciLaudiero Luisa,
Ravelli Angelo,
De Benedetti Fabrizio,
Nicolai Rebecca
Publication year - 2019
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.40800
Subject(s) - juvenile dermatomyositis , biopsy , muscle biopsy , pathology , medicine , dermatomyositis , proinflammatory cytokine , biology , inflammation
Objective To evaluate the expression of type I interferon ( IFN α/β)– and type II IFN ( IFN γ)–inducible genes in muscle biopsy specimens from patients with juvenile dermatomyositis ( DM ) and to correlate their expression levels with histologic and clinical features. Methods Expression levels of IFN ‐inducible genes and proinflammatory cytokines were assessed by quantitative polymerase chain reaction in muscle biopsy specimens from patients with juvenile DM (n = 39), patients with Duchenne's muscular dystrophy ( DMD ), and healthy controls. Muscle biopsy sections were stained and scored for severity of histopathologic features. The charts of patients with juvenile DM were reviewed for clinical features at the time of sampling and long‐term outcomes. Results Muscle expression levels of IFN α/β‐inducible genes (type I IFN score), IFN γ, IFN γ‐inducible genes (type II IFN score), and tumor necrosis factor ( TNF ) were significantly higher in juvenile DM patients not receiving glucocorticoid therapy before muscle biopsy (n = 27) compared to DMD patients (n = 24) (type I IFN score, P < 0.0001; type II IFN score, P < 0.001; TNF, P < 0.05) and healthy controls (n = 4) (type I IFN score, P < 0.01; type II IFN score, P < 0.01; TNF, P < 0.05). Immunofluorescence staining of muscle biopsy sections from untreated juvenile DM patients showed increased immunoreactivity for IFN γ and HLA class II molecules compared to controls. Type I and type II IFN scores were correlated with typical histopathologic features of juvenile DM muscle biopsy samples, such as infiltration of endomysial CD3+ cells (type I IFN score, r = 0.68; type II IFN score, r = 0.63), perimysial CD3+ cells (type I IFN score, r = 0.59; type II IFN score, r = 0.66), CD68+ cells (type II IFN score, r = 0.46), and perifascicular atrophy (type I IFN score, r = 0.61; type II IFN score, r = 0.77). Juvenile DM patients with a high type I IFN score, a high type II IFN score, and high TNF expression levels showed more severe disease activity at biopsy ( P < 0.05). In addition, juvenile DM patients with a high type II IFN score at biopsy reached clinically inactive disease significantly later than patients with low type II IFN score (log rank chi‐square value 13.53, P < 0.001). Conclusion The increased expression of IFN ‐inducible genes in the muscle in juvenile DM patients and their association with histologic and clinical features further support a pathogenic role for both type I and type II IFN s in juvenile DM .