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Proteomic analysis of plasma identifies the Toll-like receptor agonists S100A8/A9 as a novel possible marker for systemic sclerosis phenotype
  1. L van Bon1,2,
  2. M Cossu1,2,
  3. A Loof3,
  4. F Gohar4,
  5. H Wittkowski4,
  6. M Vonk2,
  7. J Roth5,
  8. W van den Berg2,
  9. W van Heerde3,
  10. J C A Broen1,
  11. T R D J Radstake1
  1. 1Department of Rheumatology, Clinical Immunology and Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
  2. 2Department of Rheumatology, Nijmegen Institute for Infection, Inflammation and Immunity (N4i) & Nijmegen Center for molecular life sciences (NCMLS), Nijmegen, The Netherlands
  3. 3Central Laboratory for Haematology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  4. 4Department of Pediatric Rheumatology and Immunology, University Children's Hospital Muenster, Muenster, Germany
  5. 5Institute of Immunology, University of Muenster, Muenster, Germany
  1. Correspondence to Dr Timothy R D J Radstake, Department of Rheumatology & Clinical Immunology, Laboratory of Translational Immunology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands; T.R.D.J.Radstake{at}


Background Systemic sclerosis (SSc) is an autoimmune disease characterised by fibrosis of the skin and the internal organs. Except for anticentromere, antitopoisomerase I and antipolymerase III antibodies, there are no reliable circulating markers predicting susceptibility and internal organ complications. This study has exploited a proteome-wide profiling method with the aim to identify new markers to identify SSc phenotype.

Method 40 SSc patients were included for proteomic identification. Patients were stratified as having diffuse cutaneous SSc (dcSSc) (n=19) or limited cutaneous SSc (lcSSc) (n=21) according to the extent of skin involvement. As controls 19 healthy donors were included. Blood was drawn and plasma was stored before analysing with the SELDI-TOF-MS. For replication in serum, the cohort was extended with 60 SSc patients.

Results Proteomic analysis revealed a list of 25 masspeaks that were differentially expressed between SSc patients and healthy controls. One of the peaks was suggestive for S100A8, a masspeak we previously found in supernatant of plasmacytoid dendritic cells from SSc patients. Increased expression of S100A8/A9 in SSc patients was confirmed in replication cohort compared with controls. Intriguingly, S100A8/A9 was highest in patients with limited cutaneous SSc having lung fibrosis.

Conclusions S100A8/A9 was robustly found to be elevated in the circulation of SSc patients, suggesting its use as a biomarker for SSc lung disease and the need to further explore the role of TLR in SSc.

  • systemic sclerosis
  • proteomics
  • Toll-like receptors
  • s100A proteins

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