Methotrexate Treatment of Newly Diagnosed RA Patients Is Associated With DNA Methylation Differences at Genes Relevant for Disease Pathogenesis and Pharmacological Action
BackgroundMethotrexate (MTX) is the first line treatment of rheumatoid arthritis (RA), and methylation changes in bulk T cells have been reported after treatment with MTX. We have investigated cell-type specific DNA methylation changes across the genome in naïve and memory CD4+ T cells before and af...
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2021
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oai:doaj.org-article:378fc971d1b14ca1be320098ff49f2fa2021-11-18T11:07:33ZMethotrexate Treatment of Newly Diagnosed RA Patients Is Associated With DNA Methylation Differences at Genes Relevant for Disease Pathogenesis and Pharmacological Action1664-322410.3389/fimmu.2021.713611https://doaj.org/article/378fc971d1b14ca1be320098ff49f2fa2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.713611/fullhttps://doaj.org/toc/1664-3224BackgroundMethotrexate (MTX) is the first line treatment of rheumatoid arthritis (RA), and methylation changes in bulk T cells have been reported after treatment with MTX. We have investigated cell-type specific DNA methylation changes across the genome in naïve and memory CD4+ T cells before and after MTX treatment of RA patients. DNA methylation profiles of newly diagnosed RA patients (N=9) were assessed by reduced representation bisulfite sequencing.ResultsWe found that MTX treatment significantly influenced DNA methylation levels at multiple CpG sites in both cell populations. Interestingly, we identified differentially methylated sites annotated to two genes; TRIM15 and SORC2, previously reported to predict treatment outcome in RA patients when measured in bulk T cells. Furthermore, several of the genes, including STAT3, annotated to the significant CpG sites are relevant for RA susceptibility or the action of MTX.ConclusionWe detected CpG sites that were associated with MTX treatment in CD4+ naïve and memory T cells isolated from RA patients. Several of these sites overlap genetic regions previously associated with RA risk and MTX treatment outcome.Kari GuderudKari GuderudLine H. SundeLine H. SundeSiri T. FlåmSiri T. FlåmMarthe T. MæhlenMaria D. MjaavattenEllen S. NorliIda M. EvenrødBettina K. AndreassenSören FranzenburgAndre FrankeSimon RaynerKristina GervinKristina GervinKristina GervinBenedicte A. LieBenedicte A. LieFrontiers Media S.A.articleRheumatoid arthritisT cellsCD4 memoryCD4 naïveDNA methylationRRBSImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021) |
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DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Rheumatoid arthritis T cells CD4 memory CD4 naïve DNA methylation RRBS Immunologic diseases. Allergy RC581-607 |
| spellingShingle |
Rheumatoid arthritis T cells CD4 memory CD4 naïve DNA methylation RRBS Immunologic diseases. Allergy RC581-607 Kari Guderud Kari Guderud Line H. Sunde Line H. Sunde Siri T. Flåm Siri T. Flåm Marthe T. Mæhlen Maria D. Mjaavatten Ellen S. Norli Ida M. Evenrød Bettina K. Andreassen Sören Franzenburg Andre Franke Simon Rayner Kristina Gervin Kristina Gervin Kristina Gervin Benedicte A. Lie Benedicte A. Lie Methotrexate Treatment of Newly Diagnosed RA Patients Is Associated With DNA Methylation Differences at Genes Relevant for Disease Pathogenesis and Pharmacological Action |
| description |
BackgroundMethotrexate (MTX) is the first line treatment of rheumatoid arthritis (RA), and methylation changes in bulk T cells have been reported after treatment with MTX. We have investigated cell-type specific DNA methylation changes across the genome in naïve and memory CD4+ T cells before and after MTX treatment of RA patients. DNA methylation profiles of newly diagnosed RA patients (N=9) were assessed by reduced representation bisulfite sequencing.ResultsWe found that MTX treatment significantly influenced DNA methylation levels at multiple CpG sites in both cell populations. Interestingly, we identified differentially methylated sites annotated to two genes; TRIM15 and SORC2, previously reported to predict treatment outcome in RA patients when measured in bulk T cells. Furthermore, several of the genes, including STAT3, annotated to the significant CpG sites are relevant for RA susceptibility or the action of MTX.ConclusionWe detected CpG sites that were associated with MTX treatment in CD4+ naïve and memory T cells isolated from RA patients. Several of these sites overlap genetic regions previously associated with RA risk and MTX treatment outcome. |
| format |
article |
| author |
Kari Guderud Kari Guderud Line H. Sunde Line H. Sunde Siri T. Flåm Siri T. Flåm Marthe T. Mæhlen Maria D. Mjaavatten Ellen S. Norli Ida M. Evenrød Bettina K. Andreassen Sören Franzenburg Andre Franke Simon Rayner Kristina Gervin Kristina Gervin Kristina Gervin Benedicte A. Lie Benedicte A. Lie |
| author_facet |
Kari Guderud Kari Guderud Line H. Sunde Line H. Sunde Siri T. Flåm Siri T. Flåm Marthe T. Mæhlen Maria D. Mjaavatten Ellen S. Norli Ida M. Evenrød Bettina K. Andreassen Sören Franzenburg Andre Franke Simon Rayner Kristina Gervin Kristina Gervin Kristina Gervin Benedicte A. Lie Benedicte A. Lie |
| author_sort |
Kari Guderud |
| title |
Methotrexate Treatment of Newly Diagnosed RA Patients Is Associated With DNA Methylation Differences at Genes Relevant for Disease Pathogenesis and Pharmacological Action |
| title_short |
Methotrexate Treatment of Newly Diagnosed RA Patients Is Associated With DNA Methylation Differences at Genes Relevant for Disease Pathogenesis and Pharmacological Action |
| title_full |
Methotrexate Treatment of Newly Diagnosed RA Patients Is Associated With DNA Methylation Differences at Genes Relevant for Disease Pathogenesis and Pharmacological Action |
| title_fullStr |
Methotrexate Treatment of Newly Diagnosed RA Patients Is Associated With DNA Methylation Differences at Genes Relevant for Disease Pathogenesis and Pharmacological Action |
| title_full_unstemmed |
Methotrexate Treatment of Newly Diagnosed RA Patients Is Associated With DNA Methylation Differences at Genes Relevant for Disease Pathogenesis and Pharmacological Action |
| title_sort |
methotrexate treatment of newly diagnosed ra patients is associated with dna methylation differences at genes relevant for disease pathogenesis and pharmacological action |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/378fc971d1b14ca1be320098ff49f2fa |
| work_keys_str_mv |
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