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Significance of miRNA Profile of Regulatory T Cells (Tregs) After Baricitinib Treatment in Rheumatoid Arthritis
Magdalena Massalska1, Anna Felis-Giemza2, Patrycja Gardias1
1Department of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.
Abstract:
Several studies proved that microRNA (miRNA) originated from cells or body fluids can serve as disease-specific biomarkers in many diseases, including rheumatoid arthritis (RA). In this study, we investigated the effects of Janus Kinase (JAK) selective inhibitor-baricitinib treatment on Treg populations and Treg-derived miRNA in context of basic thrombotic parameters. Blood samples from healthy controls (HCs) and RA patients were used for Treg phenotyping and miRNA detection. Thrombotic parameters were investigated in citrated plasma of RA and HCs. KEGG pathways enrichment analysis of selected four miRNAs was performed using DIANA-mirPath databases to predict the interaction between selected miRNAs and their mRNA targets. Baricitinib treatment resulted in significant CD4+Foxp3+ Treg population decrease (4.6 ± 0.4 vs. 5.6 ± 0.4; p = 0.01) and was characteristic of good responders' patient group. In this group, significantly lower expression of four miRNAs-miRNA-17, miRNA-142, miRNA-146, and miRNA-155-in comparison to moderate responders or HCs was noticed. The expression of all selected miRNA and miRNA-125 negatively correlated with antithrombin III level. KEGG analysis showed that levels of selected miRNA were strongly associated with four pathways regulating immunity and inflammation. We identified a panel of miRNA in Tregs that can serve as biomarkers of good response in baricitinib therapy.
Insights
MicroRNAs (miRNAs) from regulatory T cells (Tregs) show promise as biomarkers for baricitinib treatment response in rheumatoid arthritis (RA). Lower levels of specific miRNAs indicate a good response to JAK inhibitor therapy.
Area of Science:
- Immunology
- Molecular Biology
- Rheumatology
Background:
- MicroRNAs (miRNAs) are emerging as disease-specific biomarkers in various conditions, including rheumatoid arthritis (RA).
- Regulatory T cells (Tregs) play a crucial role in immune regulation and are implicated in autoimmune diseases like RA.
Purpose of the Study:
- To investigate the impact of Janus Kinase (JAK) selective inhibitor-baricitinib on Treg populations and their derived miRNAs in RA patients.
- To identify potential miRNA biomarkers associated with baricitinib treatment response and thrombotic parameters in RA.
Main Methods:
- Analysis of Treg populations and miRNA expression in blood samples from healthy controls (HCs) and RA patients.
- Thrombotic parameter assessment in RA and HCs.
- KEGG pathway enrichment analysis to predict miRNA-mRNA target interactions.
Main Results:
- Baricitinib treatment led to a significant decrease in CD4+Foxp3+ Treg populations, characteristic of good responders.
- Good responders exhibited significantly lower expression of miR-17, miR-142, miR-146, and miR-155 compared to moderate responders or HCs.
- Selected miRNA expression negatively correlated with antithrombin III levels and was associated with immune and inflammation pathways.
Conclusions:
- A panel of miRNAs within Tregs can serve as biomarkers for predicting a good response to baricitinib therapy in RA.
- These miRNAs are linked to pathways regulating immunity and inflammation, highlighting their role in RA pathogenesis and treatment response.
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