4.6 Article

Localization of enteroviral RNA within the pancreas in donors with T1D and T1D-associated autoantibodies

Journal

CELL REPORTS MEDICINE
Volume 2, Issue 8, Pages -

Publisher

CELL PRESS
DOI: 10.1016/j.xcrm.2021.100371

Keywords

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Funding

  1. Network for Pancreatic Organ Donors with Diabetes (nPOD) - JDRF
  2. JDRF [JDRF SRA-5-2012-516, JDRF 3-SRA-2017-492-A-N]
  3. German Research Foundation (DFG)

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A new method revealed increased virus infection in the pancreases of individuals with T1D and disease-associated autoantibodies, suggesting an association between enteroviruses, immune cell infiltration, autoimmunity, and β cell destruction in both preclinical and diagnosed cases of T1D.
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 (3 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 (3 cell destruction in both preclinical and diagnosed T1D.

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