title: A possible mechanism for endogenous activation of the type I interferon system in myositis patients with anti-Jo-1 or anti-Ro 52/anti-Ro 60 autoantibodies.
abstract: OBJECTIVE
  To investigate type I interferon (IFN) system activation and its correlation with autoantibodies and organ manifestations in polymyositis (PM), dermatomyositis (DM), and inclusion body myositis.
  
  
  METHODS
  Sera from 30 patients and 16 healthy controls, or purified IgG, were combined with material released from necrotized cells to stimulate IFNalpha production by peripheral blood mononuclear cells (PBMCs) from healthy blood donors. Muscle biopsy specimens from 25 patients and 7 healthy controls were investigated for blood dendritic cell antigen 2 (BDCA-2)-positive plasmacytoid dendritic cells (PDCs) and IFNalpha/beta-inducible myxovirus resistance 1 (MX-1) protein.
  
  
  RESULTS
  Sera from 13 patients who were positive for anti-Jo-1 or anti-Ro 52/anti-Ro 60 autoantibodies induced IFNalpha production in PBMCs when combined with necrotic cell material. In addition, IgG prepared from anti-Jo-1-positive PM sera induced IFNalpha with necrotic material, but not when the latter was treated with RNase. BDCA-2 expression in PDCs in muscle tissue was increased in PM patients with anti-Jo-1 autoantibodies, while MX-1 staining in capillaries was increased in DM patients, compared with healthy individuals. IFNalpha-inducing capacity correlated with interstitial lung disease, while MX-1 expression in the capillaries correlated with DM.
  
  
  CONCLUSIONS
  Immune complexes containing anti-Jo-1 or anti-Ro 52/anti-Ro 60 autoantibodies and RNA may act as endogenous IFNalpha inducers that activate IFNalpha production in PDCs. These PDCs could be of importance for inducing myositis, whereas in DM patients without autoantibodies the presence of MX-1 protein in capillaries suggests another cellular IFNalpha source and induction mechanism. Consequently, the type I IFN system may be of importance in both PM and DM, but via different pathways.
authors.affiliation: Uppsala University, Uppsala, Sweden.
authors.forename: Maija-Leena
authors.initials: ML
authors.lastname: Eloranta
authors.forename: Sevim
authors.initials: S
authors.lastname: Barbasso Helmers
authors.forename: Ann-Kristin
authors.initials: AK
authors.lastname: Ulfgren
authors.forename: Lars
authors.initials: L
authors.lastname: Rönnblom
authors.forename: Gunnar V
authors.initials: GV
authors.lastname: Alm
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Lundberg
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology*; D005260:Female; D006643:Histidine-tRNA Ligase / Q000276:immunology*; D006801:Humans; D007370:Interferon Type I / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009220:Myositis / Q000097:blood* / Q000276:immunology*; D020733:RNA, Small Cytoplasmic / Q000276:immunology*; D012261:Ribonucleoproteins / Q000276:immunology*; D000099207:SS-A Antigen
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D006643:Histidine-tRNA Ligase; D007370:Interferon Type I; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins; D000099207:SS-A Antigen; C116006:RO60 protein, human