Jeremy M Woodward1, Effrossyni Gkrania-Klotsas2, Anthony Yk Cordero-Ng3, Aloysious Aravinthan4, Betty N Bandoh5, Hongxiang Liu5, Susan Davies5, Hongyi Zhang3, Philip Stevenson6, Martin D Curran3, Dinakantha Kumararatne6. 1. Department of Gastroenterology and Clinical Nutrition, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Medical School, Cambridge, UK. 2. Department of Infectious Diseases, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Medical School, Cambridge, UK. 3. Public Health England, Clinical Microbiology and Public Health Laboratory, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Medical School, Cambridge, UK. 4. Department of Hepatology, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Medical School, Cambridge, UK. 5. Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Medical School, Cambridge, UK. 6. Department of Clinical Biochemistry and Immunology, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Medical School, Cambridge, UK.
Abstract
OBJECTIVES: A severe enteropathy of unknown etiology can be associated with common variable immunodeficiency (CVID). METHODS: S tool and archived small intestinal mucosal biopsies from patients with CVID enteropathy were analyzed by PCR for the presence of Norovirus RNA. The PCR products were sequenced to determine the relationship of viral isolates. Stool samples from 10 patients with CVID but no enteropathy served as controls. RESULTS: All eight patients in our CVID cohort with enteropathy showed persistent fecal excretion of Norovirus. Analysis of archived duodenal biopsies revealed a strong association between the presence of Norovirus and villous atrophy over a period of up to 8 years. Analysis of the viral isolates from each patient revealed distinct strains of genogroup II.4. Sequence analysis from consecutive biopsy specimens of one patient demonstrated persistence of the same viral strain over a 6-year period. CVID patients without enteropathy showed no evidence of Norovirus carriage. Viral clearance occurred spontaneously in one patient and followed oral Ribavirin therapy in two further patients, and resulted in complete symptomatic and histological recovery. However, Ribavirin treatment in two further patients was unsuccessful. CONCLUSIONS: Norovirus is an important pathogen for patients with CVID and a cause of CVID enteropathy, as viral clearance, symptom resolution, and histological recovery coincide. Ribavirin requires further evaluation as a potential therapy.
OBJECTIVES: A severe enteropathy of unknown etiology can be associated with common variable immunodeficiency (CVID). METHODS: S tool and archived small intestinal mucosal biopsies from patients with CVID enteropathy were analyzed by PCR for the presence of Norovirus RNA. The PCR products were sequenced to determine the relationship of viral isolates. Stool samples from 10 patients with CVID but no enteropathy served as controls. RESULTS: All eight patients in our CVID cohort with enteropathy showed persistent fecal excretion of Norovirus. Analysis of archived duodenal biopsies revealed a strong association between the presence of Norovirus and villous atrophy over a period of up to 8 years. Analysis of the viral isolates from each patient revealed distinct strains of genogroup II.4. Sequence analysis from consecutive biopsy specimens of one patient demonstrated persistence of the same viral strain over a 6-year period. CVIDpatients without enteropathy showed no evidence of Norovirus carriage. Viral clearance occurred spontaneously in one patient and followed oral Ribavirin therapy in two further patients, and resulted in complete symptomatic and histological recovery. However, Ribavirin treatment in two further patients was unsuccessful. CONCLUSIONS: Norovirus is an important pathogen for patients with CVID and a cause of CVID enteropathy, as viral clearance, symptom resolution, and histological recovery coincide. Ribavirin requires further evaluation as a potential therapy.
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