Rheumatology International

, Volume 39, Issue 3, pp 469–478 | Cite as

Circulating S100 proteins effectively discriminate SLE patients from healthy controls: a cross-sectional study

  • Barbora Šumová
  • Lucie Andrés Cerezo
  • Lenka Szczuková
  • Lucie Nekvindová
  • Michal Uher
  • Hana Hulejová
  • Radka Moravcová
  • Mariam Grigorian
  • Karel Pavelka
  • Jiří Vencovský
  • Ladislav Šenolt
  • Jakub ZávadaEmail author
Observational Research


S100 proteins are currently being investigated as potential diagnostic and prognostic biomarkers of several cancers and inflammatory diseases. The aims of this study were to analyse the plasma levels of S100A4, S100A8/9 and S100A12 in patients with incomplete systemic lupus erythematosus (iSLE), in patients with established SLE and in healthy controls (HCs) and to investigate the potential utility of the S100 proteins as diagnostic or activity-specific biomarkers in SLE. Plasma levels were measured by ELISA in a cross-sectional cohort study of 44 patients with SLE, 8 patients with iSLE and 43 HCs. Disease activity was assessed using the SLEDAI-2K. The mean levels of all S100 proteins were significantly higher in SLE patients compared to HCs. In iSLE patients, the levels of S100A4 and S100A12 but not S100A8/9 were also significantly higher compared to HCs. There were no significant differences in S100 levels between the iSLE and SLE patients. Plasma S100 proteins levels effectively discriminated between SLE patients and HCs. The area under the curve (AUC) for S100A4, S100A8/9 and S100A12 plasma levels was 0.989 (95% CI 0.976–1.000), 0.678 (95% CI 0.563–0.792) and 0.807 (95% CI 0.715–0.899), respectively. S100 levels did not differentiate between patients with high and low disease activity. Only the S100A12 levels were significantly associated with SLEDAI-2K and with cSLEDAI-2K. S100 proteins were significantly higher in SLE patients compared HCs and particularly S100A4 could be proposed as a potential diagnostic biomarker for SLE.


Biomarkers SLE S100 proteins Disease activity 



Anti-nuclear antibodies


Anti-double-stranded DNA antibody


British Isles Lupus Assessment Group disease activity index


Confidence interval


Systemic lupus erythematosus Disease Activity Index 2000 clinical items


Damage-associated molecular patterns


Enzyme-linked immunosorbent assay


Epithelial–mesenchymal transition




Healthy controls






Line immunoassay


Receiver operating characteristic


Standard deviation


Systemic lupus erythematosus


Systemic Lupus Erythematosus Disease Activity Index 2000


Systemic Lupus International Collaborating Clinics/American College of Rheumatology


Rheumatoid arthritis


The receptor for advanced glycation end product



We would like to thank Milada Lösterová for the excellent work as a study nurse in the management of the study.

Author contributions

Substantial contributions to the conception or design of the work: BS, MG, JZ, LS, LAC, KP, JV. Substantial contributions to the acquisition, analysis, or interpretation of data for the work: BS, HH, JZ, LS, LSz, LN, MU, LAC, JV. Drafting the work or revising it critically for important intellectual content: BS, HH, MG, LS, JZ, LSz, LN, MU, LAC, KP, JV. Final approval of the version to be published: BS, HH, MG, JZ, LS, LSz, LN, MU, LAC, KP, JV. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: BS, HH, MG, JZ, LS, LSz, LN, MU, LAC, KP, JV.


This study was supported by the project of the Ministry of Health of the Czech Republic for conceptual development of research organization [Grant no. 00023728].

Compliance with ethical standards

Conflict of interest

The authors declare no competing interests.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and bits later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute of RheumatologyPragueCzech Republic
  2. 2.Department of Rheumatology, First Faculty of MedicineCharles UniversityPragueCzech Republic
  3. 3.Institute of Biostatistics and Analyses, Faculty of MedicineMasaryk UniversityBrnoCzech Republic
  4. 4.Neuro-Oncology Group, Laboratory of Neuroplasticity, Dept. of Neuroscience and Pharmacology, Faculty of Health and Medical ScienceUniversity of CopenhagenCopenhagenDenmark

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