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Analysis of miRNA Expression in Patients with Rheumatoid Arthritis during Olokizumab Treatment
Irina V Bure1, Dmitry S Mikhaylenko1,2, Ekaterina B Kuznetsova1,2
1Institute of Molecular Medicine, Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya str., 8-2, 119992 Moscow, Russia.
Abstract:
Rheumatoid arthritis (RA) is the most common autoimmune disease worldwide. Epigenetic alternations of microRNAs (miRNAs) can contribute to its pathogenesis and progression. As the first line therapy with DMARDs is not always successful, other drugs and therapeutic targets should be applied. This study aims to measure the expression level of plasma miRNAs in RA patients treated with olokizumab and to evaluate their potential as prognostic biomarkers. The expression of 9 miRNAs was quantified in 103 RA patients before treatment and at weeks 12 and 24 of olokizumab therapy by reverse transcription-polymerase chain reaction (RT-PCR) assay and analyzed in groups of responders and non-responders. Almost all miRNAs changed their expression during therapy. The ROC curve analysis of the most prominent of them together with consequent univariate and multivariate regression analysis revealed statistically significant associations with the olokizumab therapy efficiency scores for miR-26b, miR-29, miR-451, and miR-522. Therefore, these miRNAs might be a potential therapeutic response biomarker.
Insights
This study investigated plasma microRNAs (miRNAs) in rheumatoid arthritis (RA) patients treated with olokizumab. Specific miRNAs, including miR-26b, showed potential as biomarkers for predicting treatment response in RA.
Area of Science:
- Immunology
- Genetics
- Pharmacology
Background:
- Rheumatoid arthritis (RA) is a prevalent autoimmune disease with complex pathogenesis.
- Epigenetic modifications, particularly involving microRNAs (miRNAs), play a role in RA development and progression.
- Conventional disease-modifying antirheumatic drugs (DMARDs) are not universally effective, necessitating exploration of alternative therapeutic targets and biomarkers.
Purpose of the Study:
- To quantify plasma miRNA expression levels in RA patients undergoing olokizumab therapy.
- To identify potential prognostic biomarkers for predicting therapeutic response to olokizumab.
- To correlate miRNA expression changes with treatment efficacy in RA.
Main Methods:
- Plasma samples from 103 RA patients were analyzed before and during 24 weeks of olokizumab treatment.
- Reverse transcription-polymerase chain reaction (RT-PCR) was used to quantify the expression of 9 specific miRNAs.
- Statistical analyses, including ROC curve, univariate, and multivariate regression, were performed on responders and non-responders.
Main Results:
- Significant alterations in miRNA expression were observed in most miRNAs during olokizumab therapy.
- ROC curve and regression analyses identified miR-26b, miR-29, miR-451, and miR-522 as significantly associated with olokizumab efficacy.
- These specific miRNAs demonstrated potential as indicators of treatment response.
Conclusions:
- Plasma miRNAs, particularly miR-26b, miR-29, miR-451, and miR-522, may serve as valuable prognostic biomarkers for olokizumab therapy in RA patients.
- Monitoring these miRNAs could aid in personalizing RA treatment strategies.
- Further research is warranted to validate these findings and explore their clinical utility.
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