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Peripheral blood mononuclear cell proteome profile in Behçet’s syndrome

Rheumatology International volume 40, pages 65–74 (2020)Cite this article

Abstract

Behçet’s syndrome (BS) is a systemic inflammatory disorder with unknown etiology. Investigation of proteome profiles of disease specific cells facilitates our understanding of the processes and related molecular pathways, especially in disorders like BS with complex inheritance pattern and clinical heterogeneity. In the current study, we evaluated the peripheral blood mononuclear cells (PBMCs) proteome of 59 patients with BS (33 in active and 26 in inactive phases) and of 28 healthy controls using two-dimensional fluorescence difference gel electrophoresis (2D-DIGE). Differentially expressed protein spots with at least twofold and/or statistically significant change (p ≤ 0.05) between active BS vs inactive BS, and also active BS vs healthy controls were identified by mass spectrometry (MALDI-TOF/TOF). Bioinformatic analyses revealed 16 differentially expressed proteins (12 of them in active vs inactive BS comparison, whereas 11 of them for active BS vs healthy control comparison) belonging to glycolysis, cytoskeleton organization, protein folding, and regulation of blood coagulation pathways. Stathmin (active BS vs inactive BS; fourfold, active BS vs healthy control; 4.7-fold) and WD repeat-containing protein-1 (active BS vs inactive BS; 2.7-fold, active BS vs healthy control; 2.7-fold), which are cytoskeleton-related proteins, were found to be lower in active patients compared to inactive patients and healthy control. Decreased levels of calreticulin (active BS vs inactive BS; 1.29-fold) and heat shock 70 kDa protein 8 (active BS vs healthy control; 1.5-fold) which are involved in protein folding and endoplasmic reticulum (ER) stress process, were observed in patients with active phase of BS. Down-regulation of protein folding and ER stress process proteins in BS patients may further support the involvement of ER stress in BS.

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Fig. 1
Fig. 2

Abbreviations

2D-DIGE:

Two-dimensional fluorescence difference gel electrophoresis

ALDOC:

Fructose-bisphosphate aldolase C

BS:

Behçet’s syndrome

CALR:

Calreticulin

CRP:

C-reactive protein

ER:

Endoplasmic reticulum

FCN1:

Ficolin 1

FGA:

Fibrinogen alpha chain

FGB:

Fibrinogen beta chain

FLNA:

Filamin A

FUBP1:

Far upstream element-binding protein 1

HNRNPM:

Heterogeneous nuclear ribonucleoprotein M

HSPA8:

Heat shock 70 kDa protein 8

IEF:

Isoelectric focusing

MALDI-TOF/TOF MS:

Matrix-assisted laser desorption ionization time of flight mass spectrometry

MYL6:

Myosin light polypeptide 6

PBMC:

Peripheral blood mononuclear cell

PGK1:

Phosphoglycerate kinase 1

STMN:

Stathmin

TLN1:

Talin 1

TPM3:

Tropomyosin alpha-3 chain

WDR1:

WD repeat-containing protein 1

VCL:

Vinculin

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Acknowledgements

We would like to express our gratitude to Prof Dr Hasan Yazıcı for his valuable comments on research design and critical reviewing of the manuscript. We also would like to thank all patients who participated in this study, as well as the members of Division of Rheumatology, Cerrahpaşa Medical Faculty, especially Dilşen Çevirgen, for their help on collecting patients’ samples.

Funding

This work was supported by the Technological and Scientific Research Council of Turkey (Grant No: 113S904) and Istanbul Technical University, Scientific Research Fund (Grant No: 37800).

Author information

Affiliations

  1. Department of Molecular Biology-Genetics and Biotechnology, Graduate School of Science, Engineering and Technology, İstanbul Technical University, İstanbul, Turkey

    Asli Kirectepe Aydin

  2. Division of Rheumatology, Department of Internal Medicine, Cerrahpaşa Medical Faculty, İstanbul University—Cerrahpaşa, Istanbul, Turkey

    Yeşim Özgüler & Emire Seyahi

  3. Division of Ophthalmology, Department of Surgical Medicine, Cerrahpaşa Medical Faculty, İstanbul University—Cerrahpaşa, Istanbul, Turkey

    Didar Uçar

  4. Department of Medical Biology, Faculty of Medicine, Kocaeli University, Kocaeli, Turkey

    Murat Kasap & Gürler Akpınar

  5. Department of Molecular Biology and Genetics, Dr. Orhan Öcalgiray, Molecular Biology-Biotechnology and Genetics Research Centre (MOBGAM), Graduate School of Science, Engineering and Technology, Istanbul Technical University, Ayazağa Campus, 34469, Istanbul, Maslak, Turkey

    Eda Tahir Turanli

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  1. Asli Kirectepe Aydin
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  2. Yeşim Özgüler
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  3. Didar Uçar
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  4. Murat Kasap
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  5. Gürler Akpınar
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Contributions

ETT contributed to the conception and design of the study, analysis of the data, supervise the study, and critically revise the manuscript, providing financial grants for the study. AKA performed experiments, analyzed data and wrote the manuscript. YÖ and DU contributed to patient follow-up and collection of relevant biological materials. MK and GA performed experiments and did the analysis of mass spectrometer. ES contributed to the conception and design of the study and patient follow-up, and critically revise the manuscript.

Corresponding author

Correspondence to Eda Tahir Turanli.

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Conflict of interest

The authors declare that they have no conflict of interests.

Ethical approval

This study was approved by the Ethical Committee of Istanbul University, Cerrahpaşa Medical Faculty (approval number and dates: 83045809/5584, 5 March 2013).

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Kirectepe Aydin, A., Özgüler, Y., Uçar, D. et al. Peripheral blood mononuclear cell proteome profile in Behçet’s syndrome. Rheumatol Int 40, 65–74 (2020). https://doi.org/10.1007/s00296-019-04417-2

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  • DOI: https://doi.org/10.1007/s00296-019-04417-2

Keywords

  • Behçet’s syndrome
  • Proteome
  • 2D-DIGE
  • ER stress