title: Detection of Active Epstein-Barr Virus Infection in Duodenal Mucosa of Patients With Refractory Celiac Disease.
abstract: Refractory celiac disease is characterized by mucosal damage in patients with celiac disease despite a gluten-free diet. Little is known about the mechanisms that cause persistent intestinal inflammation in these patients. We performed a case-control study of 17 consecutive patients diagnosed with refractory celiac disease from 2001 through 2014 (median age, 51 y; 10 women) and 24 patients with uncomplicated celiac disease (controls) to determine whether refractory disease is associated with infection by lymphotropic oncogenic viruses. We performed real-time PCR analyses of duodenal biopsy samples from all patients to detect Epstein-Barr virus (EBV), human herpesvirus-8, and human T-cell lymphotropic virus-I, -II, or -III. We used in situ hybridization and immunohistochemical analyses to identify infected cells and viral proteins. We did not detect human herpesvirus-8 or human T-cell lymphotropic viruses in any of the biopsy specimens. However, 12 of 17 (70.5%) biopsy specimens from patients with refractory celiac disease were positive for EBV, compared with 4 of 24 (16.6%) biopsy specimens from controls (P < .001). EBV was detected in inflammatory cells and enterocytes. An analysis of latency- and replication-associated proteins confirmed active infection. Further studies are needed to determine whether EBV infection contributes to the pathogenesis of refractory celiac disease and enteropathy-associated T-cell lymphoma.
authors.affiliation: Department of Onco-Hematology, Section of Oncology, University of Pavia and Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Perfetti
authors.affiliation: Molecular Virology Unit, University of Pavia and Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Baldanti
authors.affiliation: First Department of Internal Medicine, University of Pavia and Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy.
authors.forename: Marco Vincenzo
authors.initials: MV
authors.lastname: Lenti
authors.affiliation: Department of Molecular Medicine and Anatomic Pathology section, University of Pavia and Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Vanoli
authors.affiliation: First Department of Internal Medicine, University of Pavia and Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Biagi
authors.affiliation: Molecular Virology Unit, University of Pavia and Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Gatti
authors.affiliation: Department of Molecular Medicine and Anatomic Pathology section, University of Pavia and Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Riboni
authors.affiliation: Department of Molecular Medicine and Anatomic Pathology section, University of Pavia and Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Dallera
authors.affiliation: Department of Molecular Medicine and Anatomic Pathology section, University of Pavia and Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Paulli
authors.affiliation: Department of Onco-Hematology, Section of Oncology, University of Pavia and Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Pedrazzoli
authors.affiliation: First Department of Internal Medicine, University of Pavia and Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy. Electronic address: gr.corazza@smatteo.pv.it.
authors.forename: Gino Roberto
authors.initials: GR
authors.lastname: Corazza
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D016022:Case-Control Studies; D002446:Celiac Disease / Q000150:complications* / Q000209:etiology; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D004386:Duodenum / Q000473:pathology*; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000175:diagnosis* / Q000473:pathology*; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification*; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000302:isolation & purification; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007413:Intestinal Mucosa / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D004279:DNA, Viral; D012367:RNA, Viral
keywords: Celiac Disease Complications; EATL; EBV; Risk Factor