Type 1 Diabetes Is Associated With Enterovirus Infection in Gut Mucosa
- Maarit Oikarinen1⇓,
- Sisko Tauriainen1,
- Sami Oikarinen1,
- Teemu Honkanen2,
- Pekka Collin3,
- Immo Rantala2,4,
- Markku Mäki5,6,
- Katri Kaukinen3 and
- Heikki Hyöty1,7
- 1Department of Virology, School of Medicine, University of Tampere, Tampere, Finland
- 2Department of Pathology, School of Medicine, University of Tampere, Tampere, Finland
- 3Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, and School of Medicine, University of Tampere, Tampere, Finland
- 4Department of Pathology, Centre of Laboratory Medicine, Tampere University Hospital, Tampere, Finland
- 5Pediatric Research Centre, School of Medicine, University of Tampere, Tampere, Finland
- 6Department of Pediatrics, Tampere University Hospital, Tampere, Finland
- 7Department of Clinical Microbiology, Centre of Laboratory Medicine, Tampere University Hospital, Tampere, Finland
- Corresponding author: Maarit Oikarinen, .
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.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db11-1157/-/DC1.
- Received August 18, 2011.
- Accepted December 3, 2011.
- © 2012 by the American Diabetes Association.
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