Dysregulation of the type I interferon system in adult-onset clinically amyopathic dermatomyositis has a potential contribution to the development of interstitial lung disease

Background It has been speculated that viral infection might be one of the potential aetiologies for adult-onset clinically amyopathic dermatomyositis (CADM). The molecular pathogenesis remains largely unknown. Objectives To explore whether dysregulation of the type I interferon (IFN) system is involved in the pathogenesis of CADM. Methods We studied 16 patients with CADM and compared them with healthy control subjects (n = 20) and patients with classic dermatomyositis (DM, n = 16) and polymyositis (PM, n = 16). Expressions of mRNA for serial toll-like receptor genes (TLR2, TLR3, TLR4, TLR7, TLR8 and TLR9) and type I IFN-regulated genes (IRF7, ISG15 and MxA) in peripheral blood leucocytes (PBL) were detected by real-time polymerase chain reaction analysis. The level of IFN-alpha in blood was tested by enzyme-linked immunosorbent assay. Results The mRNA expressions of TLR7, TLR9 and IRF7 were greatly elevated in the PBL from patients with CADM compared with controls. Upregulation of the ISG15 and MxA genes was detected in the PBL from patients with CADM, as well as from patients with classic DM. Among the four study groups, the overproduction of IFN-alpha in blood was most significant in the CADM group. Especially, IFN-alpha level was obviously high in the clinical interstitial lung disease (ILD) subgroup of patients with CADM. Positive correlations were found between IFN-alpha concentration and other unfavourable prognostic factors of CADM-associated ILD. Conclusions Our data suggest that the dysregulation of the type I IFN system may be implicated in CADM pathogenesis. IFN-alpha may be a useful biomarker for assessing the disease severity of CADM-associated ILD.