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Circulating miRNAs as biomarkers in the diagnosis and treatment of rheumatic diseases
Prajzlerová, Klára ; Filková, Mária (advisor) ; Hrnčíř, Zbyněk (referee) ; Procházková, Leona (referee)
Background: MicroRNAs (miRNAs) are small non-coding single-stranded RNAs involved in the posttranscriptional inhibition of gene expression and thereby regulating all cellular functions. Their dysregulation contributes to the pathophysiology of many diseases, including rheumatic diseases. MiRNAs can also be found extracellularly in body fluids and represent promising diagnostic and prognostic biomarkers. Our study aimed to investigate miRNAs as biomarkers of stage and activity and predictors of therapeutic response of two most common inflammatory rheumatic diseases: spondyloarthritis (SpA) and rheumatic arthritis (RA). Results: We found several circulating miRNAs differentially expressed in SpA patients reflecting the severity of axial involvement and/or disease activity. The decrease in circulating miR-145 in plasma of patients with ankylosing spondylitis 3 months of anti-TNF therapy predicted a good therapeutic response and low disease activity after a year of therapy. Circulating and intracellular expression of miR-125b in peripheral blood mononuclear cells (PBMC) was lower in treatment-naïve patients with early RA than in healthy controls. Baseline expression of miR-125 in PBMC predicted a (non)adequate therapeutic response. We also found the increased expression of miR-451 in PBMC in...
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New cytokines in the pathogenesis of rheumatic diseases
Filková, Mária ; Šenolt, Ladislav (advisor) ; Hrnčíř, Zbyněk (referee) ; Horák, Pavel (referee)
Background: An imbalance between pro- and anti- inflammatory cytokine activities favors the induction of autoimmunity, chronic inflammation and joint damage in patients with rheumatoid arthritis (RA). Adipokines are bioactive proteins that are important regulators of inflammation. IL-35 is a new cytokine involved in the inflammatory processes in mouse models and is of unknown function in humans. The aim of the work was to study the levels and role of several adipokines and IL-35 in the joint and blood compartment and the association with the disease activity in patients with RA or other rheumatic diseases. Results: We found increased levels of adiponectin in serum of patients with erosive osteoarthritis (OA) of the hand, differential regulation of new adipokines vaspin and omentin in synovial fluid of patients with RA compared with OA and the effect of therapy using TNFα inhibitor on the expression profile of adipokines in subcutaneous adipose tissue of RA patients. B cell depletion therapy in RA resulted in decrease of serum levels of visfatin that correlated with following change of disease activity. The levels of IL-35 in synovial fluid are significantly higher in RA than in OA and correlate with the disease activity and functional status. IL-35 subunits p35 and EBI3 are overexpressed in RA...
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New cytokines in the pathogenesis of rheumatic diseases
Filková, Mária ; Šenolt, Ladislav (advisor) ; Hrnčíř, Zbyněk (referee) ; Horák, Pavel (referee)
Background: An imbalance between pro- and anti- inflammatory cytokine activities favors the induction of autoimmunity, chronic inflammation and joint damage in patients with rheumatoid arthritis (RA). Adipokines are bioactive proteins that are important regulators of inflammation. IL-35 is a new cytokine involved in the inflammatory processes in mouse models and is of unknown function in humans. The aim of the work was to study the levels and role of several adipokines and IL-35 in the joint and blood compartment and the association with the disease activity in patients with RA or other rheumatic diseases. Results: We found increased levels of adiponectin in serum of patients with erosive osteoarthritis (OA) of the hand, differential regulation of new adipokines vaspin and omentin in synovial fluid of patients with RA compared with OA and the effect of therapy using TNFα inhibitor on the expression profile of adipokines in subcutaneous adipose tissue of RA patients. B cell depletion therapy in RA resulted in decrease of serum levels of visfatin that correlated with following change of disease activity. The levels of IL-35 in synovial fluid are significantly higher in RA than in OA and correlate with the disease activity and functional status. IL-35 subunits p35 and EBI3 are overexpressed in RA...
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