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Galectin-9 is an easy to measure biomarker for the interferon signature in systemic lupus erythematosus and antiphospholipid syndrome
  1. Lucas L van den Hoogen1,2,
  2. Joël A G van Roon1,2,
  3. Jorre S Mertens1,2,3,
  4. Judith Wienke1,
  5. Ana Pinheiro Lopes1,2,
  6. Wilco de Jager1,
  7. Marzia Rossato1,2,4,
  8. Aridaman Pandit1,2,
  9. Catharina G K Wichers1,2,
  10. Femke van Wijk1,
  11. Ruth D E Fritsch-Stork2,5,6,
  12. Timothy R D J Radstake1,2
  1. 1 Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands
  2. 2 Department of Rheumatology and Clinical Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands
  3. 3 Department of Dermatology, Radboud University Medical Centre, Nijmegen, The Netherlands
  4. 4 Department of Biotechnology, University of Verona, Verona, Italy
  5. 5 1st Medical Department, Hanusch Hospital, Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, Vienna, Austria
  6. 6 Faculty of Medicine, Sigmund Freud Private University, Vienna, Austria
  1. Correspondence to Dr Lucas L van den Hoogen, Rheumatology and Clinical Immunology, Universitair Medisch Centrum Utrecht, Utrecht 3508 GA, The Netherlands; l.l.vandenhoogen{at}


Objective The interferon (IFN) signature is related to disease activity and vascular disease in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) and represents a promising therapeutic target. Quantification of the IFN signature is currently performed by gene expression analysis, limiting its current applicability in clinical practice. Therefore, the objective of this study was to establish an easy to measure biomarker for the IFN signature.

Methods Serum levels of galectin-9, CXCL-10 (IP-10) and tumour necrosis factor receptor type II (TNF-RII) were measured in patients with SLE, SLE+APS and primary APS (PAPS) and healthy controls (n=148) after an initial screening of serum analytes in a smaller cohort (n=43). Analytes were correlated to measures of disease activity and the IFN signature. The performance of galectin-9, CXCL-10 and TNF-RII as biomarkers to detect the IFN signature was assessed by receiver operating characteristic curves.

Results Galectin-9, CXCL-10 and TNF-RII were elevated in patients with SLE, SLE+APS and PAPS (p<0.05) and correlated with disease activity and tissue factor expression. Galectin-9 correlated stronger than CXCL-10 or TNF-RII with the IFN score (r=0.70, p<0.001) and was superior to CXCL-10 or TNF-RII in detecting the IFN signature (area under the curve (AUC) 0.86). Importantly, in patients with SLE(±APS), galectin-9 was also superior to anti-dsDNA antibody (AUC 0.70), or complement C3 (AUC 0.70) and C4 (AUC 0.78) levels in detecting the IFN signature.

Conclusion Galectin-9 is a novel, easy to measure hence clinically applicable biomarker to detect the IFN signature in patients with systemic autoimmune diseases such as SLE and APS.

  • systemic lupus erythematosus
  • antiphospholipid syndrome
  • interferon signature
  • galectin-9
  • biomarker

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  • RDEF-S and TRDJR are joint senior authors.

  • Handling editor Josef S Smolen

  • Contributors All authors were involved in study design, interpretation of data, drafting of the work and gave final approval of the version published. LLvdH was involved in data collection and performed the analysis.

  • Funding This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 731944, HarmonicSS.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Medisch Ethische Toetsingscommissie Utrecht.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Original data are available upon reasonable request.

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