MicroRNA Expression Differences in Blood-Derived CD19+ B Cells of Methotrexate Treated Rheumatoid Arthritis Patients
| العنوان: | MicroRNA Expression Differences in Blood-Derived CD19+ B Cells of Methotrexate Treated Rheumatoid Arthritis Patients |
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| المؤلفون: | Simon Rayner, Siri Tennebø Flåm, Fatima Heinicke, Anna-Birgitte Aga, E.S. Norli, Espen A Haavardsholm, Siri Lillegraven, Manuela Zucknick, Johannes Breidenbach, Marthe T. Maehlen, Xiangfu Zhong, M.D. Mjaavatten, Benedicte A. Lie, Magnus Leithaug |
| المصدر: | Frontiers in Immunology Frontiers in Immunology, Vol 12 (2021) |
| بيانات النشر: | Frontiers Media SA, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | lcsh:Immunologic diseases. Allergy, rheumatoid arthritis, 0301 basic medicine, Cell type, Antigens, CD19, Immunology, methotrexate, CD19, Arthritis, Rheumatoid, 03 medical and health sciences, 0302 clinical medicine, Immune system, PRDM1, microRNA, medicine, Humans, Immunology and Allergy, Gene Regulatory Networks, B cell, Original Research, miRNA, 030203 arthritis & rheumatology, B-Lymphocytes, biology, Gene Expression Profiling, Autoantibody, Computational Biology, Disease Management, High-Throughput Nucleotide Sequencing, medicine.disease, MicroRNAs, 030104 developmental biology, medicine.anatomical_structure, Gene Expression Regulation, NGS, Rheumatoid arthritis, Cancer research, biology.protein, RNA Interference, CD19+ B cells, Disease Susceptibility, lcsh:RC581-607, Biomarkers, Immunosuppressive Agents |
| الوصف: | Rheumatoid arthritis (RA) is a complex disease with a wide range of underlying susceptibility factors. Recently, dysregulation of microRNAs (miRNAs) in RA have been reported in several immune cell types from blood. However, B cells have not been studied in detail yet. Given the autoimmune nature of RA with the presence of autoantibodies, CD19+ B cells are a key cell type in RA pathogenesis and alterations in CD19+ B cell subpopulations have been observed in patient blood. Therefore, we aimed to reveal the global miRNA repertoire and to analyze miRNA expression profile differences in homogenous RA patient phenotypes in blood-derived CD19+ B cells. Small RNA sequencing was performed on CD19+ B cells of newly diagnosed untreated RA patients (n=10), successfully methotrexate (MTX) treated RA patients in remission (MTX treated RA patients, n=18) and healthy controls (n=9). The majority of miRNAs was detected across all phenotypes. However, significant expression differences between MTX treated RA patients and controls were observed for 27 miRNAs, while no significant differences were seen between the newly diagnosed patients and controls. Several of the differentially expressed miRNAs were previously found to be dysregulated in RA including miR-223-3p, miR-486-3p and miR-23a-3p. MiRNA target enrichment analysis, using the differentially expressed miRNAs and miRNA-target interactions from miRTarBase as input, revealed enriched target genes known to play important roles in B cell activation, differentiation and B cell receptor signaling, such as STAT3, PRDM1 and PTEN. Interestingly, many of those genes showed a high degree of correlated expression in CD19+ B cells in contrast to other immune cell types. Our results suggest important regulatory functions of miRNAs in blood-derived CD19+ B cells of MTX treated RA patients and motivate for future studies investigating the interactive mechanisms between miRNA and gene targets, as well as the possible predictive power of miRNAs for RA treatment response. |
| وصف الملف: | application/pdf |
| تدمد: | 1664-3224 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2eec7ab23c2e10aea6b0cb2493728eed https://doi.org/10.3389/fimmu.2021.663736 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....2eec7ab23c2e10aea6b0cb2493728eed |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16643224 |
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