An interferon signature in the peripheral blood of dermatomyositis patients is associated with disease activity

Abstract

Recent studies have shown increased expression of interferon (IFN)-regulated genes in the peripheral blood cells of patients with systemic lupus erythematosus. A similar interferon signature has been observed in affected muscle tissue from patients with dermatomyositis (DM), but it has not yet been determined if this signature extends to the peripheral blood in DM. We performed global gene expression profiling of peripheral blood cells from adult and juvenile DM patients and healthy controls. Several interesting groups of genes were differentially expressed in DM, including genes with immune function, and others that function in muscle or are involved in mitochondrial/oxidative phosphorylation. Investigation of type I IFN-regulated transcripts revealed a striking interferon signature present in most DM patients studied. Levels of type I IFN-regulated proteins were also elevated in DM serum samples. Furthermore, both the transcript and serum protein IFN signatures were associated with disease activity. These data suggest that the IFN signature may be a useful marker for DM disease activity, and that sampling peripheral blood may be a more practical alternative to muscle biopsy for measuring this signature.

Figure 1

Gene expression patterns distinguish DM patients from normal controls. Shown are expression data from 12 patients and 15 healthy controls (in columns) for 655 genes (in rows) that were differentially expressed between DM and controls. Expression levels are represented as log₂ ratios relative to the mean expression of control subjects according to the color key provided (range of linear fold change depicted is –8 to +8). Juvenile DM patients are marked by *.

Figure 2

Elevated expression of type I IFN-regulated genes in DM. Shown in the left panel are the expression patterns of 315 IFN-regulated genes (rows) in 12 DM patients (red bars) and 15 controls (gray bars). Green bars on the right indicate genes that belong to the peripheral blood IFN signature in SLE patients. The right panel shows the expression levels of these genes in control donor PBMCs treated for 6 h in vitro with IFN-α/β or PBS control. Expression data are shown as log₂ ratios relative to the mean expression of control sub-jects (left panel) or PBS-treated controls (right panel) according to the color key provided in Figure 1.

Figure 3

Shown is a magnification of a cluster of 93 IFN-regulated genes from Figure 2 that were up-regulated in DM patients and enriched for SLE type I IFN signature genes (43 of 93 genes). Selected genes are identified on the right-hand side.

Figure 4

IFN signature genes are up-regulated in DM patients to the same degree as observed in SLE patients. Shown are IFN scores of controls (n = 15), DM patients (n = 12), and SLE patients (n = 73).

Figure 5

The IFN signature is associated with DM disease activity. Shown are IFN scores for DM patients grouped by disease activity (0 = inactive, 1 = mild activity, 2 = high activity). There were three patients in the inactive group, one patient in the mild activity group, and eight patients in the high activity group.

Figure 6

Levels of IFN-regulated serum proteins are associated with DM disease activity. Shown are the levels of three IFN-regulated proteins measured in the serum of 10 DM patients using Luminex xMAP technology. Patients are classified by disease activity as in Figure 5.