Figure 2.

Genomic identification of type 1 interferon-inducible pathway activation in dermatomyositis muscle. (a) Analysis of 22,283 gene transcript probe sets (4,904 shown after filtering; one per row) in 113 muscle biopsy samples (one per column) disclosed a cluster of type 1 interferon-inducible genes specifically and highly upregulated in dermatomyositis (DM) with perifascicular atrophy (PFA) (thin red stripe marked by an arrow). Enlargement of this arrowed region shown on the right. Red and green indicate high and low expression. IBM, inclusion body myositis; Myo, myopathies; PM, polymyositis. (b) High expression of transcripts for interferon-stimulated gene 15 (ISG15) and myxovirus resistance protein A (MxA) are extraordinarily specific to DM muscle. JDM, juvenile DM. (c) Examples of ISG15 western blots show free ISG15 (approximately 15 kDa band) and multiple ISG15 conjugated proteins (discrete bands and smear shown at higher molecular weights) in DM but not other muscle biopsy samples. Cultured human skeletal muscle cells exposed to IFNβ develop the same pattern of free and conjugated ISG15 as occurs in DM. NoTx, no treatment. (d) MxA staining of DM muscle is sometimes so impressive that it is evident on glass slides viewed without the aid of a microscope. MxA is preferentially located in perifascicular myofibers and in blood vessel walls. Adapted from [2] with permission.