1. Localization of enteroviral RNA within the pancreas in donors with T1D and T1D-associated autoantibodies
- Author
-
Shirin, Geravandi, Sarah, Richardson, Alberto, Pugliese, and Kathrin, Maedler
- Subjects
endocrine system ,coxsackievirus ,endocrine system diseases ,type 1 diabetes ,enterovirus ,autoantibodies ,autoimmunity ,nutritional and metabolic diseases ,Tissue Donors ,smFISH ,β-cell ,Diabetes Mellitus, Type 1 ,immune system diseases ,Report ,Humans ,RNA, Viral ,Lymphocytes ,T1D ,pancreas ,AAb ,Spleen - Abstract
Summary Enteroviral infections have been associated with autoimmunity and type 1 diabetes (T1D), but reliable methods to ascertain localization of single infected cells in the pancreas were missing. Using a single-molecule-based fluorescent in situ hybridization (smFISH) method, we detected increased virus infection in pancreases from organ donors with T1D and with disease-associated autoantibodies (AAb+). Although virus-positive β cells are found at higher frequency in T1D pancreases, compared to control donors, but are scarce, most virus-positive cells are scattered in the exocrine pancreas. Augmented CD45+ lymphocytes in T1D pancreases show virus positivity or localization in close proximity to virus-positive cells. Many more infected cells were also found in spleens from T1D donors. The overall increased proportion of virus-positive cells in the pancreas of AAb+ and T1D organ donors suggests that enteroviruses are associated with immune cell infiltration, autoimmunity, and β cell destruction in both preclinical and diagnosed T1D., Graphical abstract, Highlights Enterovirus-infected cells are significantly increased in AAb+ and T1D pancreases Most of the virus-positive cells are scattered within the exocrine pancreas Virus-positive β cells are rare but more in T1D compared to control donors Also elevated in T1D donors, there is more infection in spleens than in pancreases, By highly sensitive, single-molecule-based fluorescent in situ hybridization for viral RNA, Geravandi et al. found significantly increased enterovirus-infected cells in pancreases from organ donors with type 1 diabetes (T1D) and with disease-associated autoantibodies (AAb+), which were identified as exocrine, endocrine, and immune cells and scattered within the pancreas.
- Published
- 2021