Type 1 Diabetes Is Associated With Enterovirus Infection in Gut Mucosa

• Published in: Diabetes (New York, N.Y.) Vol. 61; no. 3; pp. 687 - 691
• Main Authors: Oikarinen, Maarit, Tauriainen, Sisko, Oikarinen, Sami, Honkanen, Teemu, Collin, Pekka, Rantala, Immo, Mäki, Markku, Kaukinen, Katri, Hyöty, Heikki
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.03.2012
• Subjects: Adolescent; Adult; Aged; Antibodies; Biological and medical sciences; Biopsy; Celiac disease; Diabetes; Diabetes Mellitus, Type 1 - etiology; Diabetes Mellitus, Type 1 - virology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Enterovirus; Enterovirus - isolation & purification; Enterovirus diseases; Enterovirus infections; Enterovirus Infections - complications; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Health aspects; HLA-DR Antigens - analysis; Humans; Hybridization; Immune system; In Situ Hybridization; Infections; Inflammation; Inflammatory bowel disease; Intestinal Mucosa - virology; Male; Medical sciences; Pancreas; Pathophysiology; Polymerase Chain Reaction; Risk factors; RNA, Viral - analysis; Type 1 diabetes; Endocrinopathy; Virus; Infection; Immunopathology; Digestive system; Picornaviridae; Type 1 diabetes; Mucosa; Gut; Autoimmune disease; Enterovirus
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/db11-1157

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.