Elevated Serum Interferon-α Activity in Juvenile Dermatomyositis Associations With Disease Activity at Diagnosis and After Thirty-Six Months of Therapy

Objective. Interferon-alpha (IFN alpha) has been implicated in the pathogenesis of juvenile dermatomyositis (DM). The aim of this study was to examine serum IFN alpha activity in a cohort of children with juvenile DM to determine relationships between IFN alpha 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 alpha activity was measured using a functional reporter cell assay. Results. Patients with juvenile DM had higher serum IFN alpha activity than both pediatric and adult healthy control subjects. In untreated patients, serum IFN alpha 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 alpha -308A allele was associated with higher serum IFN alpha levels only in untreated patients (P = 0.030). At 36 months, serum IFN alpha 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 alpha 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 alpha could play a role in disease initiation in juvenile DM.