Type 1 diabetes is associated with enterovirus infection in gut mucosa.
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.
Department of Virology, School of Medicine, University of Tampere, Tampere, Finland. maarit.oikarinen@uta.fi
Maarit
M
Oikarinen
Sisko
S
Tauriainen
Sami
S
Oikarinen
Teemu
T
Honkanen
Pekka
P
Collin
Immo
I
Rantala
Markku
M
Mäki
Katri
K
Kaukinen
Heikki
H
Hyöty
D000293:Adolescent; D000328:Adult; D000368:Aged; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000821:virology; D004770:Enterovirus / Q000302:isolation & purification; D004769:Enterovirus Infections / Q000150:complications*; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D017403:In Situ Hybridization; D007413:Intestinal Mucosa / Q000821:virology*; D008297:Male; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis
D006684:HLA-DR Antigens; D012367:RNA, Viral