Reduction in infectivity of endogenous transmissible spongiform encephalopathies present in blood by adsorption to selective affinity resins
Reduction in infectivity of endogenous transmissible spongiform encephalopathies present in blood by adsorption to selective affinity resins
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DOI：
10.1016/s0140-6736(06)69897-8
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发表时间：
2006-12-23
期刊：
影响因子：
168.9
通讯作者：
Rohwer, Robert G.
中科院分区：
文献类型：
--
作者：
Gregori, Luisa;Gurgel, Patrick V.;Rohwer, Robert G.
研究背景输血可引起传染性海绵状脑病（TSE）。从捐献的血液中选择性吸附病原体可能是管理这种风险的最佳方法之一。在我们的研究中，亲和树脂L13可将掺入人红细胞浓缩液中的脑源性感染性降低约4 log（10）ID（50），而其等效物L13 A则以生产规模生产，评估其去除血液中内源性TSE感染性的能力。感染的仓鼠全血在通过亲和树脂之前以全规模进行白细胞减少。全血，leucocreduced全血（挑战），并从每个流通回收的血液进行了测定通过有限稀释titration.Findings Leutcoreduction删除输入传染性的72%。99只动物中有15只受到攻击感染，而接种两种树脂最终流出物的96或100只动物中，在540天后均未出现疾病。生物测定的检测限为0中心点2感染剂量/mL。挑战感染性的总体降低超过1个中心点22 log（10）ID。结果表明亲和配体可从去白细胞全血中去除内源性TSE感染性。相同的树脂吸附正常和异常朊病毒蛋白从人类感染变异，散发性和家族性克雅氏病，在血液成分的存在下，Interpretation TSE亲和配体，当纳入适当的设备，可用于减轻风险从TSE感染的血液，血液制品，和其他材料暴露于TSE传染性。
Background Transmissible spongiform encephalopathies (TSE) can be contracted through blood transfusion. Selective adsorption of the causative agent from donated blood might be one of the best ways of managing this risk. In our study, affinity resin L13, which reduces brain-derived infectivity spiked into human red blood cell concentrate by around 4 log(10)ID(50), and its equivalent, L13A, produced on a manufacturing scale, were assessed for their ability to remove TSE infectivity endogenously present in blood.Methods 500 mL of scrapie-infected hamster whole blood was leucoreduced at full scale before passage through the affinity resins. Infectivity of whole blood, leucoreduced whole blood (challenge), and the recovered blood from each flow-through was measured by limiting dilution titration.Findings Leutcoreduction removed 72% of input infectivity. 15 of 99 animals were infected by the challenge, whereas none of the 96 or 100 animals inoculated with the final flow-throughs from either resin developed the disease after 540 days. The limit of detection of the bioassay was 0 center dot 2 infectious doses per mL. The overall reduction of the challenge infectivity was more than 1 center dot 22 log(10)ID. The results showed removal of endogenous TSE infectivity from leucoreduced whole blood by affinity ligands. The same resins adsorb normal and abnormal prion protein from human infections with variant, sporadic, and familial Creutzfeldt-jakob disease, in the presence of blood components.Interpretation TSE affinity ligands, when incorporated into appropriate devices, can be used to mitigate the risks from TSE-infected blood, blood products, and other materials exposed to TSE infectivity.