Elevated serum interferon‐α activity in juvenile dermatomyositis: Associations with disease activity at diagnosis and after thirty‐six months of therapy

Abstract

Objective. Interferon-␣ (IFN␣) has been implicated in the pathogenesis of juvenile dermatomyositis (DM). The aim of this study was to examine serum IFN␣ activity in a cohort of children with juvenile DM to determine relationships between IFN␣ and indicators of disease activity and severity.Methods. Thirty-nine children with definite/ probable juvenile DM were included in the study. Serum samples were obtained at the time of diagnosis from 18 untreated patients with juvenile DM. Second samples from 11 of these patients were obtained at 24 months, while they were receiving treatment, and third samples were obtained from 7 of these patients at 36 months. The remaining 21 children were studied 36 months after their initial diagnosis. Serum IFN␣ activity was measured using a functional reporter cell assay.Results. Patients with juvenile DM had higher serum IFN␣ activity than both pediatric and adult healthy control subjects. In untreated patients, serum IFN␣ activity was positively correlated with serum muscle enzyme levels (P < 0.05 for creatine kinase, aspartate aminotransferase, and aldolase) and inversely correlated with the duration of untreated disease (P ‫؍‬ 0.017). The tumor necrosis factor ␣ ؊308A allele was associated with higher serum IFN␣ levels only in untreated patients (P ‫؍‬ 0.030). At 36 months, serum IFN␣ levels were inversely correlated with muscle enzyme levels in those patients still requiring therapy and with the skin Disease Activity Score in those patients who had completed therapy (P ‫؍‬ 0.002).Conclusion. Serum IFN␣ activity was associated with higher serum levels of muscle-derived enzymes and a shorter duration of untreated disease in patients with newly diagnosed juvenile DM and was inversely correlated with measures of chronic disease activity at 36 months postdiagnosis. These data suggest that IFN␣ could play a role in disease initiation in juvenile DM.

The Role of Type I IFN and TNF-α in the Pathogenesis of Sarcoidosis

“…As in the example above, a positive correlation between serum IFN-α and TNF-α in SLE was observed [25]. In JDM, the TNF-α -308A allele that has been linked to higher TNF-α production [29] was associated with increased serum IFN-α levels [26,30]. In addition, besides known up-regulation of TNF-α in RA synovium, the increased expression of type I IFN has been also reported in the synovium of patients with RA [31].…”

“…A genetic association study demonstrated that the PTPN polymorphism was associated with skewing of cytokine profiles toward higher IFN-α activity and lower TNF-α levels in vivo in patients with SLE. Moreover, in untreated patients with juvenile dermatomyositis (JDM), serum IFN-α levels was shown to be associated with the TNF-α G-308A promoter polymorphism [26]. In sarcoidosis, the presence of a TNF-α -308A variant allele was also reported to be associated with the susceptibility to and risk of sarcoidosis [27,28].…”

The association between dermatomyositis and papillary thyroid cancer: a case report

“…Recently, it has been reported that serum IFN-a activity is associated with higher serum levels of muscle-derived enzymes in DM patients [10] and that genes induced by IFN-a/b are highly expressed in DM muscle biopsies compared with muscle from patients with other inflammatory myopathies [11]. Moreover, IFN-a treatment may be associated with the onset of DM [12].…”

Dermatomiosite juvenil: revisão e atualização em patogênese e tratamento

“…Interferon causes inappropriate increase in the expression of MHC-I and induces proinflammatory cytokines and chemokines (IL-5, IFN-γ) and maybe participating in the initiation of the inflammatory process, as its activity is directly correlated to a higher elevation of serum muscle enzymes and inversely with the time of non-treated disease. 18 Plasmacytoid dendritic cells, which regulate both the innate and acquired immune response, especially against virus, were equally identified in inflammatory infiltrates of JDM patients; they would lead to an increase in the production of IFN and they would be actively involved in disease progression by modulating the function of T lymphocytes in muscular blood vessels, participating in the initiation and maintenance of the characteristic autoimmune inflammatory lesions. 3,11,19,20 …”

“…It is important to point out that vasculitic lesions, calcinosis and lipodystrophy are more common in children than in adults, being more prevalent in those with the TNF-α 308A allele. 6,27,18 Calcinosis affects 30 to 70% of patients, especially in elbows and knees. It develops in up to a mean of 3.4 years after the onset of the disease and results from the accumulation of hydroxyapatite after release of mitochondrial calcium by the damaged muscle, leading to mineralization.…”