Co-Occurrence of Types 1 and 2 PrPres in Sporadic Creutzfeldt-Jakob Disease MM1
Co-Occurrence of Types 1 and 2 PrPres in Sporadic Creutzfeldt-Jakob Disease MM1
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DOI：
10.1016/j.ajpath.2010.11.069
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发表时间：
2011-03-01
影响因子：
6
通讯作者：
Kitamoto, Tetsuyuki
中科院分区：
文献类型：
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作者：
Kobayashi, Atsushi;Mizukoshi, Kenta;Kitamoto, Tetsuyuki
多态性密码子的基因型（M/M、M/V或V/V）。人朊蛋白（PrP）基因129的多态性和脑内蛋白酶耐药型（PrPres）是决定散发性克雅氏病（sCJD）临床病理表型的主要因素。根据该分子分型系统，sCJD可分为6个亚组（MM1、MM2、MV1、MV2、VV1和VV2）。除了这些纯粹的亚组，混合病例表现出混合的神经病理表型和一个以上的PrPres类型已被发现在sCJD。为了研究1型和2型PrPres在分类为MM 1的sCJD患者中的共同出现频率，我们制备了2型PrPres特异性抗体Tohoku 2（T2），其可以在蛋白酶处理后特异性检测2型PrPres的N-末端切割位点，并检查了来自23名sCJD-MM 1患者的脑样品。使用T2抗体的Western印迹分析显示，在所有sCJD-MM1脑样品中可以检测到少数2型PrPres，包括sCJD-MM2朊病毒很少积累的小脑样品。这些结果表明，1型和2型PrPres在单个sCJD-MM1患者中的共同出现是一种普遍现象。在一个单一的朊病毒株的多个PrPres片段的一般共同出现的问题的有效性，传统的分子分型系统。(Am J Pathol 2011，178：1309 - 1315; DOI：10.1016/j.ajpath.2010.11.069）
The genotype (M/M, M/V, or V/V) at polymorphic codon. 129 of the human prion protein (PrP) gene and the type (1 or 2) of protease-resistant PrP (PrPres) in the brain are major determinants of the clinico pathological phenotypes of sporadic Creutzfeldt-Jakob disease (sCJD). According to this molecular typing system, sCJD has been classified into six subgroups (MM1, MM2, MV1, MV2, VV1, and VV2). Besides these pure subgroups, mixed cases presenting mixed neuropathological phenotypes and more than one PrPres type have been found in sCJD. To investigate the frequency of the co-occurrence of types 1 and 2 PrPres in sCJD patients classified as MM1., we produced type 2 PrPres-specific antibody Tohoku 2 (T2) that can specifically detect the N-terminal cleavage site of type 2 PrPres after protease treatment and examined brain samples from 23 patients with sCJD-MM1. Western blot analysis using the T2 antibody revealed that the minority type 2 PrPres could be detected in all sCJD-MM1 brain samples including those of the cerebellum where sCJD-MM2 prions rarely accumulate. These results show that the co-occurrence of types 1 and 2 PrPres within a single sCJD-MM1 patient is a universal phenomenon. The general co-occurrence of multiple PrPres fragments within a single prion strain questions the validity of the conventional molecular typing system. (Am J Pathol 2011, 178:1309-1315; DOI: 10.1016/j.ajpath.2010.11.069)