title: Type I interferon system activation and association with disease manifestations in systemic sclerosis.
abstract: OBJECTIVE
  To study the presence of interferogenic autoantibodies in systemic sclerosis (SSc) and their correlation with clinical manifestations, serum levels of interferon alpha (IFNalpha) and chemokines of importance in the disease process.
  
  
  METHODS
  Peripheral blood mononuclear cells (PBMCs) or purified plasmacytoid dendritic cells (pDCs) from healthy donors were stimulated with sera from patients with SSc (n=70) or healthy individuals (n=30), together with necrotic or apoptotic cell material. The IFNalpha produced and serum levels of IFNalpha, IFN-inducible protein-10 (IP-10)/chemokine (C-X-C motif) ligand 10, monocyte chemoattractant protein-1 (MCP-1)/(C-C motif) ligand-2 (CCL-2), macrophage inflammatory protein-1alpha (MIP-1alpha)/CCL-3 and RANTES/CCL-5 were measured and correlated with the presence of autoantibodies and clinical manifestations in the patients with SSc.
  
  
  RESULTS
  Sera from both diffuse SSc and limited SSc contained interferogenic antibodies, which correlated with the presence of anti-ribonucleoprotein and anti-Sjögren syndrome antigen autoantibodies. The pDCs were responsible for the IFNalpha production which required interaction with FcgammaRII and endocytosis. Increased serum levels of IP-10 were associated with vascular manifestations such as cardiac involvement (p=0.027) and pulmonary arterial hypertension (p=0.036). Increased MCP-1 or IFNalpha serum levels were associated with lung fibrosis (p=0.019 and 0.048, respectively). Digital ulcers including digital loss were associated with increased serum levels of IFNalpha (p=0.029).
  
  
  CONCLUSIONS
  An activated type I IFN system previously seen in several other systemic autoimmune diseases is also present in SSc and may contribute to the vascular pathology and affect the profibrotic process.
authors.affiliation: Department of Medical Sciences, Clinical Research Department 3, Systemic Autoimmunity Group, Entrance 85, 3rd Floor, Uppsala University Hospital, Uppsala S-75185, Sweden. maija-leena.eloranta@medsci.uu.se
authors.forename: Maija-Leena
authors.initials: ML
authors.lastname: Eloranta
authors.forename: Karin
authors.initials: K
authors.lastname: Franck-Larsson
authors.forename: Tanja
authors.initials: T
authors.lastname: Lövgren
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kalamajski
authors.forename: Anders
authors.initials: A
authors.lastname: Rönnblom
authors.forename: Kristofer
authors.initials: K
authors.lastname: Rubin
authors.forename: Gunnar V
authors.initials: GV
authors.lastname: Alm
authors.forename: Lars
authors.initials: L
authors.lastname: Rönnblom
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000974:Antibodies, Antinuclear / Q000097:blood; D000936:Antigen-Antibody Complex / Q000276:immunology; D017209:Apoptosis; D001323:Autoantibodies / Q000097:blood; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis* / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000473:pathology; D009336:Necrosis; D012595:Scleroderma, Systemic / Q000276:immunology*; D055815:Young Adult
chemical_list: D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D018925:Chemokines; D016207:Cytokines; D016898:Interferon-alpha