Peripheral blood mononuclear cells are hypomethylated in active rheumatoid arthritis and methylation correlates with disease activity
Autor: | Ilka Liebold, Andreas Grützkau, Anika Göckeritz, Velia Gerl, Randall Lindquist, Eugen Feist, Michael Zänker, Thomas Häupl, Denis Poddubnyy, Jan Zernicke, Biljana Smiljanovic, Tobias Alexander, Gerd R Burmester, Steffen Gay, Bruno Stuhlmüller |
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Přispěvatelé: | University of Zurich |
Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Male
0301 basic medicine 610 Medicine & health Severity of Illness Index Peripheral blood mononuclear cell CD19 Epigenesis Genetic Flow cytometry Arthritis Rheumatoid 03 medical and health sciences 0302 clinical medicine Rheumatology Humans Medicine Pharmacology (medical) Prospective Studies Epigenetics 030203 arthritis & rheumatology medicine.diagnostic_test biology business.industry 10051 Rheumatology Clinic and Institute of Physical Medicine U937 Cells Methylation DNA Methylation Middle Aged Flow Cytometry Molecular biology 030104 developmental biology Microscopy Fluorescence Case-Control Studies DNA methylation Leukocytes Mononuclear biology.protein Female business CD8 DNA hypomethylation |
Popis: | Objective Epigenetic modifications are dynamic and influence cellular disease activity. The aim of this study was to investigate global DNA methylation in peripheral blood mononuclear cells (PBMCs) of RA patients to clarify whether global DNA methylation pattern testing might be useful in monitoring disease activity as well as the response to therapeutics. Methods Flow cytometric measurement of 5-methyl-cytosine (5′-mC) was established using the cell line U937. In the subsequent prospective study, 62 blood samples were investigated, including 17 healthy donors and 45 RA patients at baseline and after 3 months of treatment with methotrexate, the IL-6 receptor inhibitor sarilumab, and Janus kinase inhibitors. Methylation status was assessed with an anti-5′-mC antibody and analysed in PBMCs and CD4+, CD8+, CD14+ and CD19+ subsets. Signal intensities of 5′-mC were correlated with 28-joint DASs with ESR and CRP (DAS28-ESR and DAS28-CRP). Results Compared with healthy individuals, PBMCs of RA patients showed a significant global DNA hypomethylation. Signal intensities of 5′-mC correlated with transcription levels of DNMT1, DNMT3B and MTR genes involved in methylation processes. Using flow cytometry, significant good correlations and linear regression values were achieved in RA patients between global methylation levels and DAS28-ESR values for PBMCs (r = −0.55, P = 0.002), lymphocytes (r = −0.57, P = 0.001), CD4+ (r = −0.57, P = 0.001), CD8+ (r = −0.54, P = 0.001), CD14+ (r = −0.49, P = 0.008) and CD19+ (r = −0.52, P = 0.004) cells. Conclusions The degree of global DNA methylation was found to be associated with disease activity. Based on this novel approach, the degree of global methylation is a promising biomarker for therapy monitoring and the prediction of therapy outcome in inflammatory diseases. |
Databáze: | OpenAIRE |
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