Department of Gastroenterology and Clinical Nutrition, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Medical School, Cambridge, UK.
Department of Infectious Diseases, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Medical School, Cambridge, UK.
Am J Gastroenterol. 2015 Feb;110(2):320-7. doi: 10.1038/ajg.2014.432. Epub 2015 Jan 27.
A severe enteropathy of unknown etiology can be associated with common variable immunodeficiency (CVID).
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.
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.
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.
一种病因不明的严重肠病可与普通可变免疫缺陷（CVID）有关。
通过 PCR 分析 CVID 肠病患者的工具和存档的小肠黏膜活检标本，以检测诺如病毒 RNA 的存在。对 PCR 产物进行测序，以确定病毒分离株的关系。10 例无肠病的 CVID 患者的粪便样本作为对照。
我们的 CVID 肠病队列中的所有 8 例患者均持续排出诺如病毒粪便。对十二指肠活检标本的分析显示，诺如病毒的存在与长达 8 年的绒毛萎缩之间存在很强的相关性。对每位患者分离株的分析显示，存在 II.4 基因型的不同毒株。对一名患者连续活检标本的序列分析显示，同一种病毒株持续存在 6 年。无肠病的 CVID 患者未发现诺如病毒携带。1 例患者自发清除病毒，2 例患者进一步接受利巴韦林口服治疗后病毒清除，症状和组织学完全缓解。然而，另外 2 例患者的利巴韦林治疗无效。
诺如病毒是 CVID 患者的重要病原体，也是 CVID 肠病的病因，因为病毒清除、症状缓解和组织学恢复同时发生。利巴韦林作为一种潜在的治疗方法需要进一步评估。
