No evidence of enteroviruses in the intestine of patients with type 1 diabetes.
OBJECTIVE
The purpose of this study was to investigate whether the gut mucosa is a reservoir for enterovirus persistence in patients with type 1 diabetes.


METHODS
Small intestine biopsy samples from 25 individuals at different stages of type 1 diabetes, 21 control individuals and 27 individuals with coeliac disease were analysed for the presence of enterovirus RNA by using both radioactive in-situ hybridisation and real-time RT-PCR and for the presence of enterovirus proteins by immunostaining with antibodies against VP1 and VP4-2-3 capsid proteins and virus polymerase. Lymphocytic enteropathy and serum anti-VP1 antibodies were also evaluated at the time of biopsy. Moreover, high-throughput sequencing was performed to identify viral transcripts or genomes.


RESULTS
Enterovirus was not detected by in-situ hybridisation or RT-PCR in any of the individuals tested. Immunohistology revealed a few stained cells in the intestinal epithelium in a low number of individuals, with no difference between diabetic and non-diabetic individuals. Levels of serum IgG against VP1 did not differ between control individuals and those with diabetes or coeliac disease and no evidence of diabetes-related lymphocytic enteropathy was detected. High-throughput sequencing did not reveal specific enterovirus sequences in the gut mucosa of individuals with type 1 diabetes.


CONCLUSIONS
Prolonged/persistent enterovirus infections in gut mucosa are not common in patients with type 1 diabetes.
Diabetes Research Institute, HSR-DRI, San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy.
A
A
Mercalli
V
V
Lampasona
K
K
Klingel
L
L
Albarello
C
C
Lombardoni
J
J
Ekström
V
V
Sordi
A
A
Bolla
A
A
Mariani
D
D
Bzhalava
J
J
Dillner
M
M
Roivainen
E
E
Bosi
L
L
Piemonti
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000473:pathology / Q000821:virology; D004770:Enterovirus / Q000302:isolation & purification*; D004769:Enterovirus Infections / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007413:Intestinal Mucosa / Q000473:pathology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014779:Virus Replication; D055815:Young Adult
D012367:RNA, Viral