4.7 Article

Detection of a Low-Grade Enteroviral Infection in the Islets of Langerhans of Living Patients Newly Diagnosed With Type 1 Diabetes

Journal

DIABETES
Volume 64, Issue 5, Pages 1682-1687

Publisher

AMER DIABETES ASSOC
DOI: 10.2337/db14-1370

Keywords

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Funding

  1. Academy of Finland [255770, 132362]
  2. South-Eastern Norway Regional Health Authority
  3. Novo Nordisk Foundation
  4. PEVNET (Persistent Virus Infection in Diabetes Network) Study Group - European Union [261441 PEVNET]
  5. nPOD, a collaborative type 1 diabetes research project
  6. JDRF
  7. Swedish Medical Research Council [VR K2011-65X-12219-15-6]
  8. Diabetes Wellness Foundation
  9. Novo Nordisk Fonden [NNF14OC0010935] Funding Source: researchfish
  10. Academy of Finland (AKA) [132362, 255770, 132362, 255770] Funding Source: Academy of Finland (AKA)

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The Diabetes Virus Detection study (DiViD) is the first to examine fresh pancreatic tissue at the diagnosis of type 1 diabetes for the presence of viruses. Minimal pancreatic tail resection was performed 39 weeks after onset of type 1 diabetes in six adult patients (age 24-35 years). The presence of enteroviral capsid protein 1 (VP1) and the expression of class I HLA were investigated by immunohistochemistry. Enterovirus RNA was analyzed from isolated pancreatic islets and from fresh-frozen whole pancreatic tissue using PCR and sequencing. Nondiabetic organ donors served as controls. VP1 was detected in the islets of all type 1 diabetic patients (two of nine controls). Hyperexpression of class I HLA molecules was found in the islets of all patients (one of nine controls). Enterovirus-specific RNA sequences were detected in four of six patients (zero of six controls). The results were confirmed in various laboratories. Only 1.7% of the islets contained VP1(+) cells, and the amount of enterovirus RNA was low. The results provide evidence for the presence of enterovirus in pancreatic islets of type 1 diabetic patients, which is consistent with the possibility that a low-grade enteroviral infection in the pancreatic islets contributes to disease progression in humans.

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