Prevalent abnormal prion protein in human appendixes after bovine spongiform encephalopathy epizootic: large scale survey.
Prevalent abnormal prion protein in human appendixes after bovine spongiform encephalopathy epizootic: large scale survey.
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DOI：
10.1136/bmj.f5675
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发表时间：
2013-10-15
期刊：
影响因子：
--
通讯作者：
Brandner S
中科院分区：
文献类型：
--
作者：
Gill ON;Spencer Y;Richard-Loendt A;Kelly C;Dabaghian R;Boyes L;Linehan J;Simmons M;Webb P;Bellerby P;Andrews N;Hilton DA;Ironside JW;Beck J;Poulter M;Mead S;Brandner S
目的对存档的阑尾样本进行进一步调查，以更好地了解牛海绵状脑病流行后现有的朊病毒亚临床感染流行率估计之间的差异，并了解是否有更广泛的出生队列受到影响，并更好地了解血液和血液制品管理以及手术器械处理的意义。设计对存档的附录样本进行不可逆、不关联和匿名的大规模调查。存档的附录样本来自参与早期调查的41家英国医院的病理学部门，以及参与该调查水平较低地区的其他医院。标本32441份存档附录标本用福尔马林固定，石蜡包埋，检测异常朊蛋白（PrP）的存在。结果32 441份阑尾样本中有16份PrP异常阳性，总体患病率为493 /百万人（95%置信区间282 ~ 801 /百万人）。1941-60年出生的人的患病率（733 /百万人，269 - 1596 /百万人）与1961 - 1985年出生的人的患病率（412 /百万人，198 - 758 /百万人）没有显著差异，并且在性别和三个广泛的地理区域取样中都是相似的。PRNP密码子129基因型阳性标本的基因型检测结果显示，与正常人群相比，缬氨酸纯合的比例较高，与临床确诊的vCJD病例形成鲜明对比，均为PRNP密码子129的蛋氨酸纯合。结论本研究证实了先前的研究，提示PrP异常感染的患病率很高，与迄今为止的177例vCJD病例相比，这表明人群中存在vCJD携带者的状态。这些发现对血液和血液制品的管理以及手术器械的处理具有重要意义。
Objectives To carry out a further survey of archived appendix samples to understand better the differences between existing estimates of the prevalence of subclinical infection with prions after the bovine spongiform encephalopathy epizootic and to see whether a broader birth cohort was affected, and to understand better the implications for the management of blood and blood products and for the handling of surgical instruments. Design Irreversibly unlinked and anonymised large scale survey of archived appendix samples. Setting Archived appendix samples from the pathology departments of 41 UK hospitals participating in the earlier survey, and additional hospitals in regions with lower levels of participation in that survey. Sample 32 441 archived appendix samples fixed in formalin and embedded in paraffin and tested for the presence of abnormal prion protein (PrP). Results Of the 32 441 appendix samples 16 were positive for abnormal PrP, indicating an overall prevalence of 493 per million population (95% confidence interval 282 to 801 per million). The prevalence in those born in 1941-60 (733 per million, 269 to 1596 per million) did not differ significantly from those born between 1961 and 1985 (412 per million, 198 to 758 per million) and was similar in both sexes and across the three broad geographical areas sampled. Genetic testing of the positive specimens for the genotype at PRNP codon 129 revealed a high proportion that were valine homozygous compared with the frequency in the normal population, and in stark contrast with confirmed clinical cases of vCJD, all of which were methionine homozygous at PRNP codon 129. Conclusions This study corroborates previous studies and suggests a high prevalence of infection with abnormal PrP, indicating vCJD carrier status in the population compared with the 177 vCJD cases to date. These findings have important implications for the management of blood and blood products and for the handling of surgical instruments.
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影响因子：
3.5
作者：
Mead, Simon;Uphill, James;Collinge, John
通讯作者：
Collinge, John
影响因子：
5.4
作者：
KASCSAK, RJ;RUBENSTEIN, R;DIRINGER, H
通讯作者：
DIRINGER, H
影响因子：
56.9
作者：
Beringue, Vincent;Herzog, Laetitia;Laude, Hubert
通讯作者：
Laude, Hubert
影响因子：
64.8
作者：
Collinge, J;Sidle, KCL;Hill, AF
通讯作者：
Hill, AF
影响因子：
--
作者：
Ironside, JW;Bishop, MT;Hilton, DA
通讯作者：
Hilton, DA