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Human enterovirus species B in ileocecal Crohn's disease
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
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2013 (English)In: Clinical and Translational Gastroenterology, ISSN 2155-384X, E-ISSN 2155-384X, Vol. 4, e38Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES:

Advanced ileocecal Crohn's disease (ICD) is characterized by strictures, inflammation in the enteric nervous system (myenteric plexitis), and a high frequency of NOD2 mutations. Recent findings implicate a role of NOD2 and another CD susceptibility gene, ATG16L1, in the host response against single-stranded RNA (ssRNA) viruses. However, the role of viruses in CD is unknown. We hypothesized that human enterovirus species B (HEV-B), which are ssRNA viruses with dual tropism both for the intestinal epithelium and the nervous system, could play a role in ICD.

METHODS:

We used immunohistochemistry and in situ hybridization to study the general presence of HEV-B and the presence of the two HEV-B subspecies, Coxsackie B virus (CBV) and Echovirus, in ileocecal resections from 9 children with advanced, stricturing ICD and 6 patients with volvulus, and in intestinal biopsies from 15 CD patients at the time of diagnosis.

RESULTS:

All patients with ICD had disease-associated polymorphisms in NOD2 or ATG16L1. Positive staining for HEV-B was detected both in the mucosa and in myenteric nerve ganglia in all ICD patients, but in none of the volvulus patients. Expression of the cellular receptor for CBV, CAR, was detected in nerve cell ganglia.

CONCLUSIONS:

The common presence of HEV-B in the mucosa and enteric nervous system of ICD patients in this small cohort is a novel finding that warrants further investigation to analyze whether HEV-B has a role in disease onset or progress. The presence of CAR in myenteric nerve cell ganglia provides a possible route of entry for CBV into the enteric nervous system.

Place, publisher, year, edition, pages
2013. Vol. 4, e38
National Category
Basic Medicine Gastroenterology and Hepatology
Research subject
Pathology
Identifiers
URN: urn:nbn:se:uu:diva-224046DOI: 10.1038/ctg.2013.7PubMedID: 23804031OAI: oai:DiVA.org:uu-224046DiVA: diva2:714989
Funder
Swedish Research CouncilSwedish Cancer SocietySwedish Childhood Cancer Foundation
Note

De två sista författarna delar sistaförfattarskapet.

Available from: 2014-04-30 Created: 2014-04-30 Last updated: 2017-12-05Bibliographically approved

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Nyström, NiklasSkog, OskarHansson, IngaFrisk, GunJuko-Pecirep, IvanaNilsson, MatsGyllensten, UlfWanders, Alkwin

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