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

  • Observational Research
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Abstract

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.

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Abbreviations

ANA:

Anti-nuclear antibodies

anti-dsDNA:

Anti-double-stranded DNA antibody

BILAG:

British Isles Lupus Assessment Group disease activity index

CI:

Confidence interval

c-SLEDAI-2 K:

Systemic lupus erythematosus Disease Activity Index 2000 clinical items

DAMPs:

Damage-associated molecular patterns

ELISA:

Enzyme-linked immunosorbent assay

EMT:

Epithelial–mesenchymal transition

GC:

Glucocorticoids

HCs:

Healthy controls

IF:

Immunofluorescence

IS:

Immunosuppressants

LIA:

Line immunoassay

ROC:

Receiver operating characteristic

SD:

Standard deviation

SLE:

Systemic lupus erythematosus

SLEDAI-2K:

Systemic Lupus Erythematosus Disease Activity Index 2000

SLICC/ACR:

Systemic Lupus International Collaborating Clinics/American College of Rheumatology

RA:

Rheumatoid arthritis

RAGE:

The receptor for advanced glycation end product

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Acknowledgements

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

Funding

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].

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Authors and Affiliations

  1. Institute of Rheumatology, Prague, Czech Republic

    Barbora Šumová, Lucie Andrés Cerezo, Hana Hulejová, Radka Moravcová, Karel Pavelka, Jiří Vencovský, Ladislav Šenolt & Jakub Závada

  2. Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic

    Radka Moravcová, Karel Pavelka, Jiří Vencovský, Ladislav Šenolt & Jakub Závada

  3. Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic

    Lenka Szczuková, Lucie Nekvindová & Michal Uher

  4. Neuro-Oncology Group, Laboratory of Neuroplasticity, Dept. of Neuroscience and Pharmacology, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark

    Mariam Grigorian

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  1. Barbora Šumová
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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.

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Correspondence to Jakub Závada.

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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.

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

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Šumová, B., Cerezo, L.A., Szczuková, L. et al. Circulating S100 proteins effectively discriminate SLE patients from healthy controls: a cross-sectional study. Rheumatol Int 39, 469–478 (2019). https://doi.org/10.1007/s00296-018-4190-2

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