Downregulation of Tumour Necrosis Factor α Gene Expression in Peripheral Blood Mononuclear Cells Cultured in the Presence of Tofacitinib Prior to Therapy Is Associated with Clinical Remission in Patients with Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by pain, synovial hyperplasia, mononuclear cell infiltration, bone erosion and joint destruction. Efficacy of personalized therapy in RA is associated with correct choice of therapeutic agent and a possibility to predict its e...
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MDPI AG
2022-04-01
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| Series: | Current Issues in Molecular Biology |
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| Online Access: | https://www.mdpi.com/1467-3045/44/5/132 |
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| author | Elena V. Tchetina Galina A. Markova Azamat M. Satybaldyev Aleksandr M. Lila |
| author_facet | Elena V. Tchetina Galina A. Markova Azamat M. Satybaldyev Aleksandr M. Lila |
| author_sort | Elena V. Tchetina |
| collection | DOAJ |
| description | Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by pain, synovial hyperplasia, mononuclear cell infiltration, bone erosion and joint destruction. Efficacy of personalized therapy in RA is associated with correct choice of therapeutic agent and a possibility to predict its effect prior to treatment. Our objective was to examine the association of baseline expression of metalloproteinase (MMP)-9 and cathepsin K, which are involved in cartilage and bone degradation, as well as proinflammatory cytokines tumour necrosis factor (TNF)α and interleukin (IL)-1β in the peripheral blood mononuclear cells (PBMCs) obtained from patients with RA cultured with tofacitinib (TFCN) and remission achievement. We examined 12 tofacitinib-naïve patients with RA, with a median age of 51 years and disease duration of 37.6 months. After three months of TFCN therapy, six of these patients reached clinical remission criteria while others preserved high and moderate disease activity. PBMCs were tested prior to therapy followed by their isolation in Ficoll density gradient and cultured with 100 nM TFCN for 48 h. Gene expression analysis for MMP-9, cathepsin K, IL-1β, and TNFα was performed with quantitative real-time RT-PCR using total RNA isolated from and cultured with TFCN PBMCs compared with untreated cells. Expression of all the examined genes was significantly upregulated in those cultured with TFCN PBMCs from patients who maintained high and moderate disease activity after TFCN therapy while TNFα gene expression was significantly downregulated in patients who gained remission compared with untreated counterparts. Downregulation of TNFα gene expression in PBMCs from TFCN-naïve patients with RA cultured with TFCN prior to therapy compared with untreated counterparts might serve a prognostic biomarker for remission attainment in response to tofacitinib therapy. |
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| spelling | doaj.art-f02cd6b9ff004726a9589fb941cf7dca2023-11-23T10:32:11ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452022-04-014451941194910.3390/cimb44050132Downregulation of Tumour Necrosis Factor α Gene Expression in Peripheral Blood Mononuclear Cells Cultured in the Presence of Tofacitinib Prior to Therapy Is Associated with Clinical Remission in Patients with Rheumatoid ArthritisElena V. Tchetina0Galina A. Markova1Azamat M. Satybaldyev2Aleksandr M. Lila3Immunology & Molecular Biology Laboratory, Nasonova Research Institute of Rheumatology, 115522 Moscow, RussiaImmunology & Molecular Biology Laboratory, Nasonova Research Institute of Rheumatology, 115522 Moscow, RussiaEarly Rheumatoid Arthritis Department, Nasonova Research Institute of Rheumatology, 115522 Moscow, RussiaEarly Rheumatoid Arthritis Department, Nasonova Research Institute of Rheumatology, 115522 Moscow, RussiaRheumatoid arthritis (RA) is a chronic inflammatory disease characterized by pain, synovial hyperplasia, mononuclear cell infiltration, bone erosion and joint destruction. Efficacy of personalized therapy in RA is associated with correct choice of therapeutic agent and a possibility to predict its effect prior to treatment. Our objective was to examine the association of baseline expression of metalloproteinase (MMP)-9 and cathepsin K, which are involved in cartilage and bone degradation, as well as proinflammatory cytokines tumour necrosis factor (TNF)α and interleukin (IL)-1β in the peripheral blood mononuclear cells (PBMCs) obtained from patients with RA cultured with tofacitinib (TFCN) and remission achievement. We examined 12 tofacitinib-naïve patients with RA, with a median age of 51 years and disease duration of 37.6 months. After three months of TFCN therapy, six of these patients reached clinical remission criteria while others preserved high and moderate disease activity. PBMCs were tested prior to therapy followed by their isolation in Ficoll density gradient and cultured with 100 nM TFCN for 48 h. Gene expression analysis for MMP-9, cathepsin K, IL-1β, and TNFα was performed with quantitative real-time RT-PCR using total RNA isolated from and cultured with TFCN PBMCs compared with untreated cells. Expression of all the examined genes was significantly upregulated in those cultured with TFCN PBMCs from patients who maintained high and moderate disease activity after TFCN therapy while TNFα gene expression was significantly downregulated in patients who gained remission compared with untreated counterparts. Downregulation of TNFα gene expression in PBMCs from TFCN-naïve patients with RA cultured with TFCN prior to therapy compared with untreated counterparts might serve a prognostic biomarker for remission attainment in response to tofacitinib therapy.https://www.mdpi.com/1467-3045/44/5/132rheumatoid arthritistofacitinibgene expressioncultured peripheral blood mononuclear cellsprognostic biomarkersTNFα |
| spellingShingle | Elena V. Tchetina Galina A. Markova Azamat M. Satybaldyev Aleksandr M. Lila Downregulation of Tumour Necrosis Factor α Gene Expression in Peripheral Blood Mononuclear Cells Cultured in the Presence of Tofacitinib Prior to Therapy Is Associated with Clinical Remission in Patients with Rheumatoid Arthritis Current Issues in Molecular Biology rheumatoid arthritis tofacitinib gene expression cultured peripheral blood mononuclear cells prognostic biomarkers TNFα |
| title | Downregulation of Tumour Necrosis Factor α Gene Expression in Peripheral Blood Mononuclear Cells Cultured in the Presence of Tofacitinib Prior to Therapy Is Associated with Clinical Remission in Patients with Rheumatoid Arthritis |
| title_full | Downregulation of Tumour Necrosis Factor α Gene Expression in Peripheral Blood Mononuclear Cells Cultured in the Presence of Tofacitinib Prior to Therapy Is Associated with Clinical Remission in Patients with Rheumatoid Arthritis |
| title_fullStr | Downregulation of Tumour Necrosis Factor α Gene Expression in Peripheral Blood Mononuclear Cells Cultured in the Presence of Tofacitinib Prior to Therapy Is Associated with Clinical Remission in Patients with Rheumatoid Arthritis |
| title_full_unstemmed | Downregulation of Tumour Necrosis Factor α Gene Expression in Peripheral Blood Mononuclear Cells Cultured in the Presence of Tofacitinib Prior to Therapy Is Associated with Clinical Remission in Patients with Rheumatoid Arthritis |
| title_short | Downregulation of Tumour Necrosis Factor α Gene Expression in Peripheral Blood Mononuclear Cells Cultured in the Presence of Tofacitinib Prior to Therapy Is Associated with Clinical Remission in Patients with Rheumatoid Arthritis |
| title_sort | downregulation of tumour necrosis factor α gene expression in peripheral blood mononuclear cells cultured in the presence of tofacitinib prior to therapy is associated with clinical remission in patients with rheumatoid arthritis |
| topic | rheumatoid arthritis tofacitinib gene expression cultured peripheral blood mononuclear cells prognostic biomarkers TNFα |
| url | https://www.mdpi.com/1467-3045/44/5/132 |
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