Article Text

PDF
Extended report
IFNα and its response proteins, IP-10 and SIGLEC-1, are biomarkers of disease activity in systemic lupus erythematosus
  1. Thomas Rose1,
  2. Andreas Grützkau2,
  3. Heike Hirseland2,
  4. Dörte Huscher1,2,
  5. Cornelia Dähnrich3,
  6. Andrzej Dzionek4,
  7. Tobias Ozimkowski4,
  8. Wolfgang Schlumberger3,
  9. Philipp Enghard2,
  10. Andreas Radbruch2,
  11. Gabriela Riemekasten1,
  12. Gerd-Rüdiger Burmester1,
  13. Falk Hiepe1,2,
  14. Robert Biesen1
  1. 1Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany
  2. 2German Rheumatism Research Center Berlin, Leibniz Institute, Berlin, Germany
  3. 3EUROIMMUN Medizinische Labordiagnostika AG, Lübeck, Germany
  4. 4Department of Research and Development, Miltenyi Biotec GmbH, Gladbach, Germany
  1. Correspondence to Dr Falk Hiepe, Department of Rheumatology and Clinical Immunology, Charité University Hospital, Charitéplatz 1, Berlin D-10117, Germany; falk.hiepe{at}charite.de

Abstract

Objectives To evaluate and compare the clinical efficacy of three biomarkers for interferon (IFN) activity (measured directly and indirectly) and six traditional biomarkers in indicating current and prospective disease activity (DA) in systemic lupus erythematosus (SLE).

Methods IFNα (dissociation-enhanced lanthanide fluorescent immunoassay), IFNγ-inducible protein 10 (IP-10) (ELISA) and sialic acid-binding Ig-like lectin 1 (SIGLEC-1) (flow cytometry) were measured in 79 accurately characterised patients with lupus and compared with serum titres of Anti-dsDNA (ELISA and radioimmunoassay), Anti-dsDNA-NcX ELISA, Anti-Nuc ELISA, and complement C3 and C4. DA was evaluated using the British Isles Lupus Assessment Group 2004 Index (BILAG-2004) and a modified SLE Disease Activity Index-2000 (mSLEDAI-2K). In addition, 31 clinically quiescent patients were monitored for flares over the course of 180 days.

Results Increased levels of IFNα, IP-10 and SIGLEC-1 were found in 32%, 50% and 86%, respectively, of 66 patients with active SLE. IFNα (r=0.45; p<0.0001) and SIGLEC-1 (r=0.54; p<0.0001) correlated better with BILAG-2004 than did IP-10 (r=0.38; p=0.0002), Farr assay (r=0.40; p=0.0001), Anti-dsDNA-NcX ELISA (r=0.28; p=0.0061), Anti-dsDNA ELISA (r=0.31; p=0.0025), Anti-Nuc ELISA (r=0.25; p=0.0121), C3 (r=−0.43; p<0.0001) and C4 (r=−0.33; p=0.0013). Predictors of SLE flares were disease duration ≤92 months, mild clinical activity (in contrast with no activity), complement C3≤89 mg/dl and IFNα≥20 pg/ml, while only lymphocyte count and age were independent predictors in multivariate analysis.

Conclusions IFNα, IP-10 and SIGLEC-1 emerged as beneficial biomarkers of DA in patients with SLE. Therefore the implementation of IFN biomarkers in standard lupus diagnostics should be reappraised, especially in view of emerging anti-IFN-directed therapies.

  • Autoantibodies
  • Chemokines
  • Cytokines
  • Systemic Lupus Erythematosus

Statistics from Altmetric.com

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.