Differential DNA methylation patterns in whole blood from ACPA-positive patients with DMARD-naïve rheumatoid arthritis at clinical disease onset
ObjectiveEpigenetic DNA imprints are increasingly being recognized as co-drivers of disease in complex conditions. In this exploratory and hypothesis-generating epigenome-wide association study (EWAS), we investigated differential methylation patterns in peripheral blood leucocytes from patients wit...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1488161/full |
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| author | Anders Jørgen Svendsen Anders Jørgen Svendsen Jonas Mengel-From Peter Junker Christine Dalgård George Davey Smith George Davey Smith Caroline L. Relton Caroline L. Relton Hannah R. Elliott Hannah R. Elliott Kirsten Kyvik Hanne Lindegaard Anne Friesgaard Christensen Qihua Tan Qihua Tan |
| author_facet | Anders Jørgen Svendsen Anders Jørgen Svendsen Jonas Mengel-From Peter Junker Christine Dalgård George Davey Smith George Davey Smith Caroline L. Relton Caroline L. Relton Hannah R. Elliott Hannah R. Elliott Kirsten Kyvik Hanne Lindegaard Anne Friesgaard Christensen Qihua Tan Qihua Tan |
| author_sort | Anders Jørgen Svendsen |
| collection | DOAJ |
| description | ObjectiveEpigenetic DNA imprints are increasingly being recognized as co-drivers of disease in complex conditions. In this exploratory and hypothesis-generating epigenome-wide association study (EWAS), we investigated differential methylation patterns in peripheral blood leucocytes from patients with early untreated ACPA-positive rheumatoid arthritis (RA) versus controls.MethodsWhole blood DNA was isolated from 101 disease-modifying anti-rheumatic drug (DMARD)-naïve patients with recent clinical onset of ACPA-positive RA and 200 controls. DNA methylation was studied using the Illumina MethylationEPIC BeadChips (Illumina). We assessed our findings against previously reported differentially methylated DNA positions associated with RA including an EWAS on peripheral blood leucocytes from a similar Drop Nordic cohort.ResultsWe identified 16,583 CpG sites and 14 differentially methylated regions (DMRs) associated with RA. The most robust DMRs were in the gene body of LAMP1 and the TNSF14 GENE known as LIGHT. We identified three novel Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, the taste transduction pathway, the olfactory pathway, and the viral carcinogenesis pathway, which have not previously been associated with RA. We replicated 2,248 CpG sites reported earlier in an EWAS on peripheral blood leukocytes from RA patients of Scandinavian ancestry with incipient untreated ACPA-positive disease.ConclusionWe have detected a considerable number of epigenetic marks with potential relevance to the pathogenesis of RA. These findings may pave the way for the development of narrowly targeted new drugs and possibly assist to retrieve persons at particular risk of acquiring RA. |
| format | Article |
| id | doaj-art-8cefce4e163f452387ea96633a4b15bd |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-8cefce4e163f452387ea96633a4b15bd2025-08-20T03:13:27ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.14881611488161Differential DNA methylation patterns in whole blood from ACPA-positive patients with DMARD-naïve rheumatoid arthritis at clinical disease onsetAnders Jørgen Svendsen0Anders Jørgen Svendsen1Jonas Mengel-From2Peter Junker3Christine Dalgård4George Davey Smith5George Davey Smith6Caroline L. Relton7Caroline L. Relton8Hannah R. Elliott9Hannah R. Elliott10Kirsten Kyvik11Hanne Lindegaard12Anne Friesgaard Christensen13Qihua Tan14Qihua Tan15Research Unit for Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, DenmarkDepartment of Internal Medicine & Emergency, Odense University Hospital, Svendborg, DenmarkUnit of Human Genetics, Department of Clinical Research, University of Southern Denmark, Odense, DenmarkDepartment of Rheumatology, Odense University Hospital, Odense, DenmarkClinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, DenmarkMRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, United KingdomPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, United KingdomMRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, United KingdomPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, United KingdomMRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, United KingdomPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, United KingdomResearch Unit of Clinical Genetics, University of Southern Denmark, Odense, DenmarkDepartment of Rheumatology, Odense University Hospital, Odense, DenmarkDepartment of Internal Medicine, Lillebaelt Hospital, Kolding, DenmarkResearch Unit for Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, DenmarkUnit of Human Genetics, Department of Clinical Research, University of Southern Denmark, Odense, DenmarkObjectiveEpigenetic DNA imprints are increasingly being recognized as co-drivers of disease in complex conditions. In this exploratory and hypothesis-generating epigenome-wide association study (EWAS), we investigated differential methylation patterns in peripheral blood leucocytes from patients with early untreated ACPA-positive rheumatoid arthritis (RA) versus controls.MethodsWhole blood DNA was isolated from 101 disease-modifying anti-rheumatic drug (DMARD)-naïve patients with recent clinical onset of ACPA-positive RA and 200 controls. DNA methylation was studied using the Illumina MethylationEPIC BeadChips (Illumina). We assessed our findings against previously reported differentially methylated DNA positions associated with RA including an EWAS on peripheral blood leucocytes from a similar Drop Nordic cohort.ResultsWe identified 16,583 CpG sites and 14 differentially methylated regions (DMRs) associated with RA. The most robust DMRs were in the gene body of LAMP1 and the TNSF14 GENE known as LIGHT. We identified three novel Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, the taste transduction pathway, the olfactory pathway, and the viral carcinogenesis pathway, which have not previously been associated with RA. We replicated 2,248 CpG sites reported earlier in an EWAS on peripheral blood leukocytes from RA patients of Scandinavian ancestry with incipient untreated ACPA-positive disease.ConclusionWe have detected a considerable number of epigenetic marks with potential relevance to the pathogenesis of RA. These findings may pave the way for the development of narrowly targeted new drugs and possibly assist to retrieve persons at particular risk of acquiring RA.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1488161/fullrheumatoid arthritisanti-CCP antibodiesepigeneticsDNA-methylationincidence |
| spellingShingle | Anders Jørgen Svendsen Anders Jørgen Svendsen Jonas Mengel-From Peter Junker Christine Dalgård George Davey Smith George Davey Smith Caroline L. Relton Caroline L. Relton Hannah R. Elliott Hannah R. Elliott Kirsten Kyvik Hanne Lindegaard Anne Friesgaard Christensen Qihua Tan Qihua Tan Differential DNA methylation patterns in whole blood from ACPA-positive patients with DMARD-naïve rheumatoid arthritis at clinical disease onset Frontiers in Immunology rheumatoid arthritis anti-CCP antibodies epigenetics DNA-methylation incidence |
| title | Differential DNA methylation patterns in whole blood from ACPA-positive patients with DMARD-naïve rheumatoid arthritis at clinical disease onset |
| title_full | Differential DNA methylation patterns in whole blood from ACPA-positive patients with DMARD-naïve rheumatoid arthritis at clinical disease onset |
| title_fullStr | Differential DNA methylation patterns in whole blood from ACPA-positive patients with DMARD-naïve rheumatoid arthritis at clinical disease onset |
| title_full_unstemmed | Differential DNA methylation patterns in whole blood from ACPA-positive patients with DMARD-naïve rheumatoid arthritis at clinical disease onset |
| title_short | Differential DNA methylation patterns in whole blood from ACPA-positive patients with DMARD-naïve rheumatoid arthritis at clinical disease onset |
| title_sort | differential dna methylation patterns in whole blood from acpa positive patients with dmard naive rheumatoid arthritis at clinical disease onset |
| topic | rheumatoid arthritis anti-CCP antibodies epigenetics DNA-methylation incidence |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1488161/full |
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