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Beyond PrP9res) type 1/type 2 dichotomy in Creutzfeldt-Jakob disease.

Uro-Coste E, Cassard H, Simon S, Lugan S, Bilheude JM, Perret-Liaudet A, Ironside JW, Haik S, Basset-Leobon C, Lacroux C, Peoch' K, Streichenberger N, Langeveld J, Head MW, Grassi J, Hauw JJ, Schelcher F, Delisle MB, Andréoletti O - PLoS Pathog. (2008)

Bottom Line: However, since cases of CJD show co-occurrence of type 1 and type 2 PrP(res) in the brain, the basis of this classification system and its relationship to agent strain are under discussion.In 30% of cases, both type 1 and type 2 PrP(res) were identified.Despite this, the other two biochemical assays found that PrP(Sc) from an individual patient demonstrated uniform biochemical properties.

View Article: PubMed Central - PubMed

Affiliation: INSERM U858, Institut de Médecine Moléculaire de Rangueil and Service d'Anatomie Pathologique et Histologie-Cytologie, C.H.U. Rangueil, Toulouse, France.

ABSTRACT
Sporadic Creutzfeldt-Jakob disease (sCJD) cases are currently subclassified according to the methionine/valine polymorphism at codon 129 of the PRNP gene and the proteinase K (PK) digested abnormal prion protein (PrP(res)) identified on Western blotting (type 1 or type 2). These biochemically distinct PrP(res) types have been considered to represent potential distinct prion strains. However, since cases of CJD show co-occurrence of type 1 and type 2 PrP(res) in the brain, the basis of this classification system and its relationship to agent strain are under discussion. Different brain areas from 41 sCJD and 12 iatrogenic CJD (iCJD) cases were investigated, using Western blotting for PrP(res) and two other biochemical assays reflecting the behaviour of the disease-associated form of the prion protein (PrP(Sc)) under variable PK digestion conditions. In 30% of cases, both type 1 and type 2 PrP(res) were identified. Despite this, the other two biochemical assays found that PrP(Sc) from an individual patient demonstrated uniform biochemical properties. Moreover, in sCJD, four distinct biochemical PrP(Sc) subgroups were identified that correlated with the current sCJD clinico-pathological classification. In iCJD, four similar biochemical clusters were observed, but these did not correlate to any particular PRNP 129 polymorphism or western blot PrP(res) pattern. The identification of four different PrP(Sc) biochemical subgroups in sCJD and iCJD, irrespective of the PRNP polymorphism at codon 129 and the PrP(res) isoform provides an alternative biochemical definition of PrP(Sc) diversity and new insight in the perception of Human TSE agents variability.

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PrPres Profiles in sCJD Patients.(A) PrPres from cerebellum (lane 1), caudate nucleus (lane 2), frontal cortex (lane 3) and occipital cortex (lane 4) of a single MV patient was extracted and submitted to WB. Detection with antibody Sha31 reveals different PrPres profiles. (B–D) PrPres in cerebellum from seven different patients using Sha31 mAb (B), 8G8 mAb (C), and 12B2 mAb (D). Because of their epitope, Sha31 and 8G8 can detect both type 1 and type 2 PrPres while 12B2 detects type 1 only. Lane 1, MM patient; lane 2, MV patient; lane 3, VV patient; lane 4, MV patient; lane 5, MV patient; lane 6, VV patient; lane 7, MM patient; line 8, sheep BSE control. (E, F) PrPres profile in temporal cortex from three MV patients revealed by Sha31 mAb (E) or 12B2 mAb (F).
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ppat-1000029-g001: PrPres Profiles in sCJD Patients.(A) PrPres from cerebellum (lane 1), caudate nucleus (lane 2), frontal cortex (lane 3) and occipital cortex (lane 4) of a single MV patient was extracted and submitted to WB. Detection with antibody Sha31 reveals different PrPres profiles. (B–D) PrPres in cerebellum from seven different patients using Sha31 mAb (B), 8G8 mAb (C), and 12B2 mAb (D). Because of their epitope, Sha31 and 8G8 can detect both type 1 and type 2 PrPres while 12B2 detects type 1 only. Lane 1, MM patient; lane 2, MV patient; lane 3, VV patient; lane 4, MV patient; lane 5, MV patient; lane 6, VV patient; lane 7, MM patient; line 8, sheep BSE control. (E, F) PrPres profile in temporal cortex from three MV patients revealed by Sha31 mAb (E) or 12B2 mAb (F).

Mentions: For each sCJD case, PrPres profile was determined from five brain areas using both Sha31 and 8G8 antibodies. A single PrPres type (type 1 or type 2) was observed in investigated brain areas of most of the MM1 (n = 11), and all the areas from MV1 (n = 8), VV1 (n = 1) and MM2 (n = 3) sCJD cases of our panel. However, in several cases initially classified as MM1 (n = 2), and in a majority of VV2 (n = 5) or MV2 (n = 6) cases, some brain areas harboured mixed electrophoretic pattern characterized by two distinct bands at 19 and 21 kDa, indicating the coexistence of PrPres type 1 and type 2 (Table 1 and Figure 1A). Moreover, in individual patients some brain areas were found to be type 1, while another area could be found to be type 2 (Table 1 and Figure 1A). Since both Sha31 and 8G8 gave similar results this phenomenon cannot be attributed to some antibody peculiarity in PrP recognition (Figure 1B and 1C).


Beyond PrP9res) type 1/type 2 dichotomy in Creutzfeldt-Jakob disease.

Uro-Coste E, Cassard H, Simon S, Lugan S, Bilheude JM, Perret-Liaudet A, Ironside JW, Haik S, Basset-Leobon C, Lacroux C, Peoch' K, Streichenberger N, Langeveld J, Head MW, Grassi J, Hauw JJ, Schelcher F, Delisle MB, Andréoletti O - PLoS Pathog. (2008)

PrPres Profiles in sCJD Patients.(A) PrPres from cerebellum (lane 1), caudate nucleus (lane 2), frontal cortex (lane 3) and occipital cortex (lane 4) of a single MV patient was extracted and submitted to WB. Detection with antibody Sha31 reveals different PrPres profiles. (B–D) PrPres in cerebellum from seven different patients using Sha31 mAb (B), 8G8 mAb (C), and 12B2 mAb (D). Because of their epitope, Sha31 and 8G8 can detect both type 1 and type 2 PrPres while 12B2 detects type 1 only. Lane 1, MM patient; lane 2, MV patient; lane 3, VV patient; lane 4, MV patient; lane 5, MV patient; lane 6, VV patient; lane 7, MM patient; line 8, sheep BSE control. (E, F) PrPres profile in temporal cortex from three MV patients revealed by Sha31 mAb (E) or 12B2 mAb (F).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2279301&req=5

ppat-1000029-g001: PrPres Profiles in sCJD Patients.(A) PrPres from cerebellum (lane 1), caudate nucleus (lane 2), frontal cortex (lane 3) and occipital cortex (lane 4) of a single MV patient was extracted and submitted to WB. Detection with antibody Sha31 reveals different PrPres profiles. (B–D) PrPres in cerebellum from seven different patients using Sha31 mAb (B), 8G8 mAb (C), and 12B2 mAb (D). Because of their epitope, Sha31 and 8G8 can detect both type 1 and type 2 PrPres while 12B2 detects type 1 only. Lane 1, MM patient; lane 2, MV patient; lane 3, VV patient; lane 4, MV patient; lane 5, MV patient; lane 6, VV patient; lane 7, MM patient; line 8, sheep BSE control. (E, F) PrPres profile in temporal cortex from three MV patients revealed by Sha31 mAb (E) or 12B2 mAb (F).
Mentions: For each sCJD case, PrPres profile was determined from five brain areas using both Sha31 and 8G8 antibodies. A single PrPres type (type 1 or type 2) was observed in investigated brain areas of most of the MM1 (n = 11), and all the areas from MV1 (n = 8), VV1 (n = 1) and MM2 (n = 3) sCJD cases of our panel. However, in several cases initially classified as MM1 (n = 2), and in a majority of VV2 (n = 5) or MV2 (n = 6) cases, some brain areas harboured mixed electrophoretic pattern characterized by two distinct bands at 19 and 21 kDa, indicating the coexistence of PrPres type 1 and type 2 (Table 1 and Figure 1A). Moreover, in individual patients some brain areas were found to be type 1, while another area could be found to be type 2 (Table 1 and Figure 1A). Since both Sha31 and 8G8 gave similar results this phenomenon cannot be attributed to some antibody peculiarity in PrP recognition (Figure 1B and 1C).

Bottom Line: However, since cases of CJD show co-occurrence of type 1 and type 2 PrP(res) in the brain, the basis of this classification system and its relationship to agent strain are under discussion.In 30% of cases, both type 1 and type 2 PrP(res) were identified.Despite this, the other two biochemical assays found that PrP(Sc) from an individual patient demonstrated uniform biochemical properties.

View Article: PubMed Central - PubMed

Affiliation: INSERM U858, Institut de Médecine Moléculaire de Rangueil and Service d'Anatomie Pathologique et Histologie-Cytologie, C.H.U. Rangueil, Toulouse, France.

ABSTRACT
Sporadic Creutzfeldt-Jakob disease (sCJD) cases are currently subclassified according to the methionine/valine polymorphism at codon 129 of the PRNP gene and the proteinase K (PK) digested abnormal prion protein (PrP(res)) identified on Western blotting (type 1 or type 2). These biochemically distinct PrP(res) types have been considered to represent potential distinct prion strains. However, since cases of CJD show co-occurrence of type 1 and type 2 PrP(res) in the brain, the basis of this classification system and its relationship to agent strain are under discussion. Different brain areas from 41 sCJD and 12 iatrogenic CJD (iCJD) cases were investigated, using Western blotting for PrP(res) and two other biochemical assays reflecting the behaviour of the disease-associated form of the prion protein (PrP(Sc)) under variable PK digestion conditions. In 30% of cases, both type 1 and type 2 PrP(res) were identified. Despite this, the other two biochemical assays found that PrP(Sc) from an individual patient demonstrated uniform biochemical properties. Moreover, in sCJD, four distinct biochemical PrP(Sc) subgroups were identified that correlated with the current sCJD clinico-pathological classification. In iCJD, four similar biochemical clusters were observed, but these did not correlate to any particular PRNP 129 polymorphism or western blot PrP(res) pattern. The identification of four different PrP(Sc) biochemical subgroups in sCJD and iCJD, irrespective of the PRNP polymorphism at codon 129 and the PrP(res) isoform provides an alternative biochemical definition of PrP(Sc) diversity and new insight in the perception of Human TSE agents variability.

Show MeSH
Related in: MedlinePlus