title: Dysregulation of the type I interferon system in adult-onset clinically amyopathic dermatomyositis has a potential contribution to the development of interstitial lung disease.
abstract: 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.
  
  
  OBJECTIVE
  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-α 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-α in blood was most significant in the CADM group. Especially, IFN-α level was obviously high in the clinical interstitial lung disease (ILD) subgroup of patients with CADM. Positive correlations were found between IFN-α 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-α may be a useful biomarker for assessing the disease severity of CADM-associated ILD.
authors.affiliation: The Division of Rheumatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: W C
authors.initials: WC
authors.lastname: Sun
authors.forename: Y C
authors.initials: YC
authors.lastname: Sun
authors.forename: H
authors.initials: H
authors.lastname: Lin
authors.forename: B
authors.initials: B
authors.lastname: Yan
authors.forename: G X
authors.initials: GX
authors.lastname: Shi
mesh_terms: D000328:Adult; D017668:Age of Onset; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D003882:Dermatomyositis / Q000097:blood* / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics; D007370:Interferon Type I / Q000097:blood*; D017563:Lung Diseases, Interstitial / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D017285:Polymyositis / Q000097:blood / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012720:Severity of Illness Index; D013223:Statistics as Topic; D051193:Toll-Like Receptors / Q000235:genetics
chemical_list: D015415:Biomarkers; D050835:Interferon Regulatory Factors; D007370:Interferon Type I; D051193:Toll-Like Receptors