Session Title: Pediatric Rheumatology – Pathogenesis and Genetics Poster
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
There is growing evidence for an involvement of interferons (IFNs) in the chronic inflammation that characterizes juvenile dermatomyositis (JDM). The aim of this study was to investigate muscle expression of type I (IFNα/β) and type II (IFNγ) IFN inducible genes in muscle biopsies of JDM patients and their correlations with clinical and histological aspects of the disease.
Methods: In a retrospective cohort of patients diagnosed with JDM (n=35), expression of the six genes part of the so called type I IFN score (IFI27, IFI44L, IFIT1, ISG15, RSAD2, SIGLEC1), as well as of IFNγ and of CXCL9, CXCL10, CXCL11, CIITA, were analyzed by real-time PCR on snap-frozen muscle biopsies and compared with biopsies from Duchenne muscular dystrophy (DMD) patients (n=24) and 4 healthy controls (HC). Expression levels of CXCL9, CIITA (genes specifically induced by IFNγ) and IFNγ itself were used to generate a type II IFN score. We also analyzed mRNA expression of the pro-inflammatory cytokines interleukin- 1β (IL-1β), tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6). Patient charts were reviewed to record clinical features at diagnosis and long term outcomes: physician’s global assessment of disease activity, serum levels of muscle enzymes, erythrocyte sedimentation rate, C-reactive protein level, antinuclear antibodies status, time to inactive disease and time to prednisone (or equivalent) dose 0.2 mg/kg/daily, and relapses. We furthermore evaluated typical histological aspects of JDM (inflammatory infiltrate, necrosis, perifascicular atrophy and fibrosis) on tissue sections of the muscle biopsies.
Results: JDM patients treated (n=12) with systemic glucocorticoids before biopsy were excluded from analysis, because expression levels of the studied genes were markedly reduced compared to untreated patients. The type I IFN score and type II IFN score were significantly higher in the muscle of untreated JDM patients (n=23) compared with controls (p<0.0001, p<0.001 respectively). Expression of TNFα, but not of IL-1β and IL-6, was significantly (p<0.05) higher in untreated JDM muscle biopsies compared with those of controls. Type I IFN score correlated with inflammatory infiltrate and necrosis, while the type II IFN score correlated with inflammatory infiltrate, perifascicular atrophy and fibrosis. Type I IFN score, type II IFN score and TNFα expression significantly correlated with physician’s global assessment at diagnosis (r=0.38, r=0.42, r=0.62, respectively). When analyzing correlations with long term outcomes, we found that patients with elevated type II IFN score reached clinically inactive disease significantly later than patients with low type II IFN score (log-rank chi square value=10.1, p<0.01).
Conclusion: IFN type I and type II scores in muscle biopsies of JDM patients correlate with clinical and histological features suggesting a pathogenic role of IFNs in muscle damage and inflammation in JDM. Noteworthily the type II score correlated with time to clinically inactive disease, suggesting a correlation with disease severity.
To cite this abstract in AMA style:Nicolai R, Moneta GM, Rosina S, Fiorillo C, Pires Marafon D, Verardo M, Bracci Laudiero L, Minetti C, Ravelli A, De Benedetti F. Expression of Type I and Type II Interferons Is Increased in Muscle Biopsies of Juvenile Dermatomyositis Patients and Related to Clinical and Histological Features [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/expression-of-type-i-and-type-ii-interferons-is-increased-in-muscle-biopsies-of-juvenile-dermatomyositis-patients-and-related-to-clinical-and-histological-features/. Accessed September 18, 2021.
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