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Extended report
Type I interferon system activation and association with disease manifestations in systemic sclerosis
  1. Maija-Leena Eloranta1,
  2. Karin Franck-Larsson1,2,
  3. Tanja Lövgren1,
  4. Sebastian Kalamajski3,
  5. Anders Rönnblom1,
  6. Kristofer Rubin3,
  7. Gunnar V Alm4,
  8. Lars Rönnblom1
  1. 1Department of Medical Sciences, Uppsala University, Uppsala, Sweden
  2. 2Wyeth AB, Solna, Sweden
  3. 3Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
  4. 4Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden
  1. Correspondence to Dr Maija-Leena Eloranta, 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{at}


Objectives To study the presence of interferogenic autoantibodies in systemic sclerosis (SSc) and their correlation with clinical manifestations, serum levels of interferon α (IFNα) 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 IFNα produced and serum levels of IFNα, 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-1α (MIP-1α)/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 IFNα production which required interaction with FcγRII 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 IFNα 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 IFNα (p=0.029).

Conclusion 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.

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  • Funding The work was supported by grants from the Dana Foundation, the Swedish Research Council, the Swedish Society of Medicine, the Swedish Rheumatism Association, the Swedish Cancer Foundation, the Uppsala University Hospital Development Foundation, the Agnes and Mac Rudberg Foundation, the Nilsson Foundation, the King Gustaf V 80-year Foundation and COMBINE.

  • Competing interests None.

  • Ethics approval The study was approved by the ethical committee in Uppsala and informed consent was obtained from all patients and controls.