No evidence of enteroviruses in the intestine of patients with type 1 diabetes

• Published in: Diabetologia Vol. 55; no. 9; pp. 2479 - 2488
• Main Authors: Mercalli, A., Lampasona, V., Klingel, K., Albarello, L., Lombardoni, C., Ekström, J., Sordi, V., Bolla, A., Mariani, A., Bzhalava, D., Dillner, J., Roivainen, M., Bosi, E., Piemonti, L.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.09.2012; Springer; Springer Nature B.V
• Subjects: Adolescent; Adult; Aged; Antibodies; Antigens; Biological and medical sciences; Biopsy; Capsid protein; Celiac disease; Child; Child, Preschool; Clinical Medicine; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 1 - complications; Diabetes Mellitus, Type 1 - pathology; Diabetes Mellitus, Type 1 - virology; Diabetes. Impaired glucose tolerance; Digestive tract; Endocrine pancreas. Apud cells (diseases); Endocrinology and Diabetes; Endocrinopathies; Endokrinologi och diabetes; Endoscopy; Enterovirus; Enterovirus - isolation & purification; Enterovirus Infections - pathology; Epithelium; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Gastroenterology; Genomes; Hospitals; Human Physiology; Humans; Hypotheses; Immunoglobulin G; Immunohistochemistry; In Situ Hybridization; Infection; Internal Medicine; Intestinal Mucosa - pathology; Intestinal Mucosa - virology; Intestine; Klinisk medicin; Male; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Metabolic Diseases; Middle Aged; Mucosa; Polymerase chain reaction; Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA; RNA, Viral; Small intestine; Type 1 diabetes; Viral infections; Virus Replication; Viruses; VP1 protein; Young Adult; Italy; Sweden; Intestine; Type 1 diabetes; Enterovirus; Endocrinopathy; Virus; Human; Immunopathology; Digestive system; Picornaviridae; Gut; Autoimmune disease
• ISSN: 0012-186X; 1432-0428; 1432-0428
• DOI: 10.1007/s00125-012-2591-4

Aims/hypothesis 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/interpretation Prolonged/persistent enterovirus infections in gut mucosa are not common in patients with type 1 diabetes.