Epigenetic differences at immune and type 1 diabetes susceptibility genes in blood from young children after COVID-19 infection

Affiliations

¹ Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Munich, Germany.
² Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium; Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
³ Center for Regenerative Therapies Dresden, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany; Department of Paediatrics, University Hospital Carl Gustav Carus, Dresden, Germany.
⁴ Kinder- und Jugendkrankenhaus auf der Bult, Hannover, Germany.
⁵ Unit for Pediatric Endocrinology, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden; Department of Pediatrics, Skane University Hospital, Malmö/Lund, Sweden.
⁶ Department of Pediatric Diabetology and Pediatrics, The Children's Clinical Hospital Józef Polikarp Brudziński, Warsaw, Poland; Department of Pediatric Diabetology and Pediatrics, Medical University of Warsaw, Warsaw, Poland.
⁷ Centre for Human Genetics, Nuffield Department of Medicine, NIHR Biomedical Research Centre, University of Oxford, Oxford, UK.
⁸ Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Munich, Germany; Forschergruppe Diabetes, School of Medicine, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany; Forschergruppe Diabetes e.V. at Helmholtz Munich, German Research Center for Environmental Health, Munich, Germany.
⁹ Center for Regenerative Therapies Dresden, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany; Paul Langerhans Institute Dresden of Helmholtz Munich at University Hospital Carl Gustav Carus and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany. Electronic address: ezio.bonifacio@tu-dresden.de.

PMID: 40749537
DOI: 10.1016/j.jaut.2025.103468

Free article

Epigenetic differences at immune and type 1 diabetes susceptibility genes in blood from young children after COVID-19 infection

Raffael Ott et al. J Autoimmun. 2025 Sep.

Free article

. 2025 Sep:156:103468.

doi: 10.1016/j.jaut.2025.103468. Epub 2025 Jul 31.

Affiliations

¹ Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Munich, Germany.
² Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium; Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
³ Center for Regenerative Therapies Dresden, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany; Department of Paediatrics, University Hospital Carl Gustav Carus, Dresden, Germany.
⁴ Kinder- und Jugendkrankenhaus auf der Bult, Hannover, Germany.
⁵ Unit for Pediatric Endocrinology, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden; Department of Pediatrics, Skane University Hospital, Malmö/Lund, Sweden.
⁶ Department of Pediatric Diabetology and Pediatrics, The Children's Clinical Hospital Józef Polikarp Brudziński, Warsaw, Poland; Department of Pediatric Diabetology and Pediatrics, Medical University of Warsaw, Warsaw, Poland.
⁷ Centre for Human Genetics, Nuffield Department of Medicine, NIHR Biomedical Research Centre, University of Oxford, Oxford, UK.
⁸ Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Munich, Germany; Forschergruppe Diabetes, School of Medicine, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany; Forschergruppe Diabetes e.V. at Helmholtz Munich, German Research Center for Environmental Health, Munich, Germany.
⁹ Center for Regenerative Therapies Dresden, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany; Paul Langerhans Institute Dresden of Helmholtz Munich at University Hospital Carl Gustav Carus and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany. Electronic address: ezio.bonifacio@tu-dresden.de.

PMID: 40749537
DOI: 10.1016/j.jaut.2025.103468

Abstract

Background: Viral infections, including COVID-19, are associated with an increased risk for type 1 diabetes (T1D), but potential underlying mechanisms remain unexplored. We evaluated whether COVID-19 or influenza A infection is characterized by differential DNA methylation at immune and T1D susceptibility genes in young children at risk for T1D.

Methods: Epigenome-wide association analysis using the Illumina MethylationEPIC microarray was performed in blood taken at age 1.5 years (IQR, 1.49-1.52 y) from 740 prospectively followed children with increased risk of T1D. SARS-CoV-2 and influenza A H1N1 antibodies were monitored at 2-4-month intervals from age 6 months to identify infection.

Results: COVID-19 and influenza infection occurred prior to the DNA methylation sample in 81 and 74 children, respectively. Of these, infection occurred within 3 months of the DNA methylation sample (recent infection) in 43 and 22 children. Compared to children without COVID-19 or influenza A infection, children with recent COVID-19 infection showed differential methylation at key immune- and antiviral genes, including ADAR, IFI44L, MX1 and OASL. In addition to ADAR, six further T1D susceptibility genes, including the SARS-CoV-2 cell entry receptor neuropilin-1, had differential methylation at nearby CpGs in children infected by SARS-CoV-2. A quantitatively less differential methylation was also observed in children with an earlier COVID-19 infection at some of these CpG sites. Infections with influenza showed no associations.

Conclusion: Children with SARS-CoV-2 infection showed sustained DNA methylation changes at genes critical for antiviral response and T1D susceptibility, potentially contributing to immune dysregulation and promotion of the autoimmune process underlying T1D.

Keywords: Autoimmunity; COVID-19; DNA methylation; Influenza; SARS-CoV-2; Type 1 diabetes; Viral infection.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Anette-G. Ziegler reports a relationship with Novo Nordisk that includes: consulting or advisory. Anette-G. Ziegler reports a relationship with Sanofi-Aventis that includes: consulting or advisory and speaking and lecture fees. Ezio Bonifacio reports a relationship with Sanofi-Aventis that includes: speaking and lecture fees and travel reimbursement. Helena Elding Larsson reports a relationship with Novo Nordisk that includes: speaking and lecture fees. Helena Elding Larsson reports a relationship with Sanofi-Aventis that includes: speaking and lecture fees. Gita Gemulla reports a relationship with Sanofi-Aventis that includes: speaking and lecture fees. Olga Kordonouri reports a relationship with Amgen that includes: consulting or advisory and speaking and lecture fees. Olga Kordonouri reports a relationship with Dexcom that includes: consulting or advisory and speaking and lecture fees. Olga Kordonouri reports a relationship with Diamyd Medical that includes: consulting or advisory and speaking and lecture fees. Olga Kordonouri reports a relationship with Sanofi-Aventis that includes: consulting or advisory and speaking and lecture fees. Agnieszka Szypowska reports a relationship with Synoptis Pharma that includes: speaking and lecture fees and travel reimbursement. Agnieszka Szypowska reports a relationship with Sanofi-Aventis that includes: consulting or advisory and speaking and lecture fees. Agnieszka Szypowska reports a relationship with Proglikemia that includes: consulting or advisory. Agnieszka Szypowska reports a relationship with Medtronic Poland that includes: consulting or advisory. Anette-G. Ziegler is listed as inventor for the patent "Method for determining the risk to develop type 1 diabetes” (WO 2019/002364) by Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) and Technical University of Dresden. Ezio Bonifacio is listed as inventor for the patent "Method for determining the risk to develop type 1 diabetes” (WO 2019/002364) by Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) and Technical University of Dresden. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Epigenetic differences at immune and type 1 diabetes susceptibility genes in blood from young children after COVID-19 infection

Affiliations

Epigenetic differences at immune and type 1 diabetes susceptibility genes in blood from young children after COVID-19 infection

Authors

Affiliations

Abstract

Conflict of interest statement

MeSH terms

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous