Article Text

Download PDFPDF
Extended report
The interferon type I signature is present in systemic sclerosis before overt fibrosis and might contribute to its pathogenesis through high BAFF gene expression and high collagen synthesis
  1. Zana Brkic1,
  2. Lenny van Bon2,3,
  3. Marta Cossu3,4,
  4. Cornelia G van Helden-Meeuwsen1,
  5. Madelon C Vonk3,
  6. Hanneke Knaapen3,
  7. Wim van den Berg3,
  8. Virgil A Dalm1,
  9. Paul L Van Daele1,
  10. Adriana Severino4,
  11. Naomi I Maria1,
  12. Samara Guillen1,
  13. Willem A Dik1,
  14. Lorenzo Beretta4,
  15. Marjan A Versnel1,
  16. Timothy Radstake2
  1. 1Department of Immunology, Erasmus Medical Center, Rotterdam, The Netherlands
  2. 2Department of Rheumatology, Clinical Immunology and Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
  3. 3Department of Rheumatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
  4. 4Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy
  1. Correspondence to Professor Timothy Radstake, Department of Rheumatology & Clinical Immunology, Laboratory of Translational Immunology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht 3485 CX, The Netherlands; Tradstake73{at}


Background Interferon (IFN) signature has been reported in definite systemic sclerosis (SSc) but it has not been characterised in early SSc (EaSSc). We aim at characterising IFN type I signature in SSc before overt skin fibrosis develops.

Methods The expression of 11 IFN type I inducible genes was tested in whole-blood samples from 30 healthy controls (HCs), 12 subjects with primary Raynaud's phenomenon (RP), 19 patients with EaSSc, 7 patients with definite SSc without cutaneous fibrosis, 21 limited cutaneous SSc and 10 diffuse cutaneous SSc subjects. The correlation between IFN activity in monocytes, B cell activating factor (BAFF) mRNA expression and type III procollagen N-terminal propeptide (PIIINP) serum levels was tested.

Results In all the SSc groups, higher IFN scores were observed compared with HC. An IFN score ≥7.09 discriminated HCs from patients with SSc (sensitivity=0.7, specificity=0.88, area under receiving operating characteristic (AUROC)=0.82); the prevalence of an elevated IFN score was: HC=3.3%; RP=33.3%, EaSSc=78.9%, definite SSc=100%, limited cutaneous SSc=42.9%, diffuse cutaneous SSc=70.0%. In monocytes an IFN score ≥4.12 distinguished HCs from patients with fibrotic SSc (sensitivity=0.62, specificity=0.85, AUROC=0.76). Compared with IFN-negative subjects, IFN-positive subjects had higher monocyte BAFF mRNA levels (19.7±5.2 vs 15.20±4.0, p=2.1×10−5) and serum PIIINP levels (median=6.0 (IQR 5.4–8.9) vs median=3.9 (IQR 3.3–4.7), p=0.0004).

Conclusions An IFN type I signature is observed in patients with SSc from the earliest phases of the disease, even before overt skin fibrosis. The presence of IFN type I signature in monocytes is correlated with BAFF mRNA expression and serum PIIINP levels, supporting a contribution in the pathogenesis and progression of SSc.

  • Autoimmune Diseases
  • Systemic Sclerosis
  • Inflammation
  • Cytokines

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.