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Rheumatoid Arthritis Patients, Both Newly Diagnosed and Methotrexate Treated, Show More DNA Methylation Differences in CD4+ Memory Than in CD4+ Naïve T Cells.
Guderud, Kari; Sunde, Line H; Flåm, Siri T; Mæhlen, Marthe T; Mjaavatten, Maria D; Lillegraven, Siri; Aga, Anna-Birgitte; Evenrød, Ida M; Norli, Ellen S; Andreassen, Bettina K; Franzenburg, Sören; Franke, Andre; Haavardsholm, Espen A; Rayner, Simon; Gervin, Kristina; Lie, Benedicte A.
Afiliación
  • Guderud K; Department of Medical Genetics, University of Oslo and Oslo University Hospital, Oslo, Norway.
  • Sunde LH; K. G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway.
  • Flåm ST; Department of Medical Genetics, University of Oslo and Oslo University Hospital, Oslo, Norway.
  • Mæhlen MT; K. G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway.
  • Mjaavatten MD; Department of Medical Genetics, University of Oslo and Oslo University Hospital, Oslo, Norway.
  • Lillegraven S; K. G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway.
  • Aga AB; Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.
  • Evenrød IM; Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.
  • Norli ES; Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.
  • Andreassen BK; Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.
  • Franzenburg S; Department of Medical Genetics, University of Oslo and Oslo University Hospital, Oslo, Norway.
  • Franke A; Department of Rheumatology, Martina Hansens Hospital, Bærum, Norway.
  • Haavardsholm EA; Department of Research, Cancer Registry of Norway, Institute for Population-Based Research, Oslo, Norway.
  • Rayner S; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
  • Gervin K; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
  • Lie BA; Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.
Front Immunol ; 11: 194, 2020.
Article en En | MEDLINE | ID: mdl-32117312
Background: Differences in DNA methylation have been reported in B and T lymphocyte populations, including CD4+ T cells, isolated from rheumatoid arthritis (RA) patients when compared to healthy controls. CD4+ T cells are a heterogeneous cell type with subpopulations displaying distinct DNA methylation patterns. In this study, we investigated DNA methylation using reduced representation bisulfite sequencing in two CD4+ T cell populations (CD4+ memory and naïve cells) in three groups: newly diagnosed, disease modifying antirheumatic drugs (DMARD) naïve RA patients (N = 11), methotrexate (MTX) treated RA patients (N = 18), and healthy controls (N = 9) matched for age, gender and smoking status. Results: Analyses of these data revealed significantly more differentially methylated positions (DMPs) in CD4+ memory than in CD4+ naïve T cells (904 vs. 19 DMPs) in RA patients compared to controls. The majority of DMPs (72%) identified in newly diagnosed and DMARD naïve RA patients with active disease showed increased DNA methylation (39 DMPs), whereas most DMPs (80%) identified in the MTX treated RA patients in remission displayed decreased DNA methylation (694 DMPs). Interestingly, we also found that about one third of the 101 known RA risk loci overlapped (±500 kb) with the DMPs. Notably, introns of the UBASH3A gene harbor both the lead RA risk SNP and two DMPs in CD4+ memory T cells. Conclusion: Our results suggest that RA associated DNA methylation differences vary between the two T cell subsets, but are also influenced by RA characteristics such as disease activity, disease duration and/or MTX treatment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Reumatoide / Linfocitos T CD4-Positivos / Metotrexato / Metilación de ADN / Memoria Inmunológica Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Front Immunol Año: 2020 Tipo del documento: Article País de afiliación: Noruega Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Reumatoide / Linfocitos T CD4-Positivos / Metotrexato / Metilación de ADN / Memoria Inmunológica Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Front Immunol Año: 2020 Tipo del documento: Article País de afiliación: Noruega Pais de publicación: Suiza