Type I interferon pathway in adult and juvenile dermatomyositis

Abstract

Gene expression profiling and protein studies of the type I interferon pathway have revealed important insights into the disease process in adult and juvenile dermatomyositis. The most prominent and consistent feature has been a characteristic whole blood gene signature indicating upregulation of the type I interferon pathway. Upregulation of the type I interferon protein signature has added additional markers of disease activity and insight into the pathogenesis of the disease.

Figure 1

Type I interferon-inducible genes are similarly regulated in dermatomyositis and systemic lupus erythematosus blood. Expression profiles of 191 interferon (IFN)-inducible genes (rows) in peripheral blood cells from dermatomyositis (DM) patients (n = 12) [23] and systemic lupus erythematosus (SLE) patients (n = 48) (columns). Expression levels are shown as log₂ ratios relative to healthy controls (n = 15 controls for DM subjects; n = 37 controls for SLE subjects). Right-hand panel: expression of the same set of genes in type I IFN-stimulated peripheral blood mononuclear cells from four normal donors [29]. Expression levels shown as log₂ ratios relative to PBS-treated control samples. The color scale reflects expression fold-changes from +8 (yellow) to -8 (blue). Demographics for normal donors for DM subjects: 73% (11/15) female, 80% (12/15) Caucasian, mean age 40.4 ± 11.0 years. Demographics for normal donors for SLE subjects: 100% (37/37) female, 97.3% (36/37) Caucasian, mean age 45.7 ± 6.4 years. Demographics for DM subjects: 10 adult DM and two juvenile DM, 91% Caucasian, 73% female, average age 43 ± 26 years. Demographics for SLE subjects: 97.9% (47/48) female, 45.8% (22/48) Caucasian, 41.7% (20/48) African American, mean age 41.5 ± 9.8 years.

Figure 2

Interferon gene and chemokine score distributions in adult and juvenile dermatomyositis patients not significantly different. P values calculated by Mann-Whitney test. Middle line represents the median, horizontal lines represent the minimum and maximum values, and central box represents the values from the 25th to 75th percentile. DM, dermatomyositis; IFN, interferon.