Peripheral blood mononuclear cell proteome profile in Behçet’s syndrome
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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.
KeywordsBehçet’s syndrome Proteome 2D-DIGE ER stress
Two-dimensional fluorescence difference gel electrophoresis
Fructose-bisphosphate aldolase C
Fibrinogen alpha chain
Fibrinogen beta chain
Far upstream element-binding protein 1
Heterogeneous nuclear ribonucleoprotein M
Heat shock 70 kDa protein 8
- MALDI-TOF/TOF MS
Matrix-assisted laser desorption ionization time of flight mass spectrometry
Myosin light polypeptide 6
Peripheral blood mononuclear cell
Phosphoglycerate kinase 1
Tropomyosin alpha-3 chain
WD repeat-containing protein 1
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.
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.
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).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interests.
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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