Type 1 Diabetes Is Associated With Enterovirus Infection in Gut Mucosa

  1. Heikki Hyöty1,7
  1. 1Department of Virology, School of Medicine, University of Tampere, Tampere, Finland
  2. 2Department of Pathology, School of Medicine, University of Tampere, Tampere, Finland
  3. 3Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, and School of Medicine, University of Tampere, Tampere, Finland
  4. 4Department of Pathology, Centre of Laboratory Medicine, Tampere University Hospital, Tampere, Finland
  5. 5Pediatric Research Centre, School of Medicine, University of Tampere, Tampere, Finland
  6. 6Department of Pediatrics, Tampere University Hospital, Tampere, Finland
  7. 7Department of Clinical Microbiology, Centre of Laboratory Medicine, Tampere University Hospital, Tampere, Finland
  1. Corresponding author: Maarit Oikarinen, maarit.oikarinen{at}uta.fi.

Abstract

Enterovirus infections have been linked to type 1 diabetes in several studies. Enteroviruses also have tropism to pancreatic islets and can cause β-cell damage in experimental models. Viral persistence has been suspected to be an important pathogenetic factor. This study evaluates whether gut mucosa is a reservoir for enterovirus persistence in type 1 diabetic patients. Small-bowel mucosal biopsy samples from 39 type 1 diabetic patients, 41 control subjects, and 40 celiac disease patients were analyzed for the presence of enterovirus using in situ hybridization (ISH), RT-PCR, and immunohistochemistry. The presence of virus was compared with inflammatory markers such as infiltrating T cells, HLA-DR expression, and transglutaminase 2–targeted IgA deposits. Enterovirus RNA was found in diabetic patients more frequently than in control subjects and was associated with a clear inflammation response in the gut mucosa. Viral RNA was often detected in the absence of viral protein, suggesting defective replication of the virus. Patients remained virus positive in follow-up samples taken after 12 months’ observation. The results suggest that a large proportion of type 1 diabetic patients have prolonged/persistent enterovirus infection associated with an inflammation process in gut mucosa. This finding opens new opportunities for studying the viral etiology of type 1 diabetes.

  • Received August 18, 2011.
  • Accepted December 3, 2011.

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