Enterovirus VP1 protein and HLA class I hyperexpression in pancreatic islet cells of organ donors with type 1 diabetes
We report the most extensive analysis to date of VP1 and HLA-I in pancreases from donors with preclinical and diagnosed type 1 diabetes. We find an association of VP1 with residual beta cells after diagnosis and demonstrate VP1 positivity during the autoantibody-positive preclinical stage. For the first time, we show that VP1 positivity and HLA-I hyperexpression in islet cells are both present during the preclinical stage. While the study of tissues does not allow us to demonstrate causality, our data support the hypothesis that enterovirus infections may occur throughout the natural history of type 1 diabetes and may be one of multiple mechanisms driving islet cell HLA-I hyperexpression.
Authors
- Thomas Worthington (ORCID: https://orcid.org/0000-0002-2699-2074)
- Sisko Tauriainen (ORCID: https://orcid.org/0000-0003-3423-5409)
- Jutta E. Laiho (ORCID: https://orcid.org/0000-0002-5443-4651)
- Heikki Hyöty (ORCID: https://orcid.org/0000-0003-0370-4145)
- Christine S. Flaxman (ORCID: https://orcid.org/0009-0002-1144-7767)
- Alberto Pugliese (ORCID: https://orcid.org/0000-0002-7211-0319)
- Paola S. Apaolaza (ORCID: https://orcid.org/0000-0002-7550-054X)
- Noel G. Morgan (ORCID: https://orcid.org/0000-0003-1537-8113)
- Matthias von Herrath (ORCID: https://orcid.org/0000-0002-5211-0485)
- Irina Kusmartseva (ORCID: https://orcid.org/0000-0003-2614-0813)
- Maarit Oikarinen (ORCID: https://orcid.org/0000-0003-1329-1508)
- Pouria Akhbari (ORCID: https://orcid.org/0000-0002-4127-9058)
- Sarah J. Richardson (ORCID: https://orcid.org/0000-0002-1160-6062)
- Mark A. Atkinson (ORCID: https://orcid.org/0000-0001-8489-4782)
- Teresa Rodríguez-Calvo (ORCID: https://orcid.org/0000-0003-1531-8583)
- John S. Kaddis (ORCID: https://orcid.org/0000-0002-6752-7670)
- Martha Campbell‐Thompson (ORCID: https://orcid.org/0000-0001-6878-1235)
Institutions
- University of Miami (US)
- University of Turku (FI)
- Tampere University (FI)
- Novo Nordisk (Denmark) (DK)
- University of Exeter (GB)
- Helmholtz Zentrum München (DE)
- University of Florida (US)
- City of Hope (US)
- Tampere University Hospital (FI)
- Tampere University (FI)
- Fimlab (Finland) (FI)
- Beckman Research Institute
Publication Details
- Journal
- Diabetologia
- Published
- 2025-03-16
- DOI
- https://doi.org/10.1007/s00125-025-06384-9
- Citations
- 12
- Primary Topic
- Diabetes and associated disorders
- Type
- article
- Field-Weighted Citation Impact
- 21.81
Funders
- Juvenile Diabetes Research Foundation International
- Leona M. and Harry B. Helmsley Charitable Trust
- Human Islet Research Network
- National Institute for Health and Care Research
- University of Exeter
- European Commission
- European Foundation for the Study of Diabetes
- Suomen Kulttuurirahasto
- Diabetestutkimussäätiö
- Medical Research Council
- Faculty of Medicine and Health, University of Sydney
- National Institute of Diabetes and Digestive and Kidney Diseases