AUTHOR=Paradowska-Gorycka Agnieszka , Wajda Anna , Romanowska-Próchnicka Katarzyna , Walczuk Ewa , Kuca-Warnawin Ewa , Kmiolek Tomasz , Stypinska Barbara , Rzeszotarska Ewa , Majewski Dominik , Jagodzinski Pawel Piotr , Pawlik Andrzej 

TITLE=Th17/Treg-Related Transcriptional Factor Expression and Cytokine Profile in Patients With Rheumatoid Arthritis

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.572858

DOI=10.3389/fimmu.2020.572858

ISSN=1664-3224

ABSTRACT=<sec><title>Objectives</title><p>The aim of our study was to determine whether there is a correlation between transcription factors expression and Th17/Treg ratio, cytokine profile in the RA phenotype as well as to identify transcription factors that could be a potential biomarker for RA.</p></sec><sec><title>Methods</title><p>The study was conducted on 45 patients with RA, 27 patients with OA and 46 healthy controls (HCs). Th17 and Treg frequency was determined by flow cytometry (15 patients with RA/OA and 15 subjects of HC). Gene expression was estimated by qPCR, and the serum cytokine levels were determined by ELISA.</p></sec><sec><title>Results</title><p>The percentage of Treg (CD4+CD25highCD127-) cells in RA patients was lower than in OA patients or HCs. Proportions of Th17 (CD4+CCR6+CXCR3-) cells were higher in RA and OA in comparison to HCs. <italic>STAT5</italic> showed a very high expression in the blood of RA patients compared to healthy subjects. The expression of <italic>STAT5</italic> and <italic>HELIOS</italic> was not detected in Th17 cells. A positive correlation between <italic>SMAD3</italic> and <italic>STAT3</italic> in RA patients was observed. Negative correlations between <italic>HIF-1A</italic> and <italic>SMAD2</italic> in RA Treg cells and DAS-28 score were observed. The range of serum of IL-17 and IL-21 were higher in RA patients than in OA patients. Concentrations of serum IL-2 and IFN-γ were higher in RA and OA patients than in healthy subjects. Based on the ROC analysis, the diagnostic potential of the combination of <italic>HIF1A</italic>, <italic>SMAD3</italic> and <italic>STAT3</italic>, was determined at AUC 0.95 for distinguishing RA patients from HCs. For distinguishing RA patients from OA patients the diagnostic potential of the combination of <italic>SMAD2</italic>, <italic>SMAD3</italic>, <italic>SMAD4</italic> and <italic>STAT3</italic>, was determined at AUC 0.95.</p></sec><sec><title>Conclusion</title><p>Based on our study, we conclude that <italic>SMAD3</italic> and <italic>STAT3</italic> could be potential diagnostic biomarkers for RA.</p></sec>