NR ADHI
AU Deslys,J.P.; Lasmezas,C.I.; Streichenberger,N.; Hill,A.F.; Collinge,J.; Dormont,D.; Kopp,N.
TI New variant Creutzfeldt-Jakob disease in France
QU Lancet 1997 Jan 4; 349(9044): 30-1
PT journal article
VT
All ten cases of the new variant of Creutzfeldt-Jakob disease (nvCJD) studied in the UK share a specific electrophoretic pattern of PrP-Pres,[1] the abnormal isoform of the prion protein (PrP), which is partially resistant to protease digestion and accumulates in the brain of patients during the disease. The PrP protein has two possible sites of glycosylation and the electrophoretic pattern shows three bands (corresponding to the di-, mono-, and unglycosylated forms). Under mild conditions of treatment by proteinase K, normal PrP is completely hydrolysed while only the N-terminal extremity of PrP-Pres is cleaved. The molecular weight of PrP-Pres after proteolysis is lower in nvCJD than in sporadic CJD and there is a higher proportion of the di-glycosylated form. Thus, a type of PrP-Pres has been defined according to these two parameters and appears to be specific for nvCJD.
The first patient suffering from nvCJD described in France was a 26-year-old man, homozygous for methionine at codon 129 of the PrP gene and without any known risk factor.[2] All currently known cases of nvCJD have been homozygous for methionine at codon129.[3] Pathological examination showed typical florid plaques and the PrP immunostaining pattern seen in nvCJD in the UK. We report that he also had an indistinguishable electrophoretic pattern to UK cases (type 4, figure). This result confirms the apparent great homogeneity of the nvCJD group.
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Western blot detection of PrPsc in brains from patients with CJD using PrP monoclonal antibody 3F4.
P1 patient 1 (type 4 pattern, nvCJD); P2 patient 2 (type 2 pattern); 1 sporadic CJD (type 1 pattern); 2 sporadic CJD (type 2 pattern); 3 iatrogenic CJD linked to growth hormone (type 3 pattern); 4 nvCJD from UK (type 4 pattern). All patients presented here were methionine homozygotes at codon 129 of the PrP gene except type 3 who was a valine homozygote (details of the protocol are available from the authors).
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Florid plaques were also found in a brain specimen of another French patient who was a methionine homozygote at codon 129.[4] This patient has been reported as a possible case of nvCJD even though the history of this 52-year-old woman included a dura-mater graft 11 years before. As seen in the figure, the electrophoretic pattern of this case is not a type 4 but a type 2 pattern similar to that described in an iatrogenic dura-mater linked CJD case.[1]
These findings suggest that this second French case is not nvCJD but most likely an iatrogenic case linked to the dura-mater graft. These findings indicate that the observation of a few florid plaques is insufficient for the diagnosis of nvCJD which should take into account the criteria described by Will et al as a whole, that is the clinical history, the presence of florid plaques, and the pattern of PrP-Pres deposition assessed by immunohistochemistry, together with the electrophoretic pattern of PrP-Pres. Further studies will be required to fully evaluate the specificity of molecular "strain typing" of these diseases. We thank F Lamoury for technical help and the INSERM network for providing tissue from patients. We are grateful to J Ironside who provided the UK nvCJD material.
1 Collinge J, Sidle KCL, Meads J, Ironside J, Hill AF. Molecular analysis of prion strain variation and the aetiology of "new variant" CJD. Nature 1996; 383: 685-90.
2 Chazot G, Broussolle E, Lapras C, Blätter T, Aguzzi A, Kopp N. New variant of Creutzfeldt-Jakob disease in a 26-year-old French man. Lancet 1996;347:1181.
3 Will RG, Ironside JW, Zeidler M, et al. A new variant of Creutfeldt-Jakob disease in the UK. Lancet 1996; 347: 921-25.
4 Kopp N, Streichenberger N, Deslys JP, Laplanche JL, Chazot G. Creutzfeldt-Jakob disease in a 52-year-old woman with florid plaques. Lancet 1996; 348: 1239-40.
ZR 4 Zitate
MH Adult; Brain/metabolism/pathology; Case Report; *Creutzfeldt-Jakob Syndrome/genetics/pathology; Dura Mater/transplantation; Electrophoresis; Female; Human; Male; Middle Age; Phosphoribosyl Pyrophosphate/genetics/metabolism; PrPsc Proteins/metabolism
AD Service de Neurovirologie, CEA, DSV/DRM/SSA, Fontensyzux-Roses, France.
SP englisch
PO England
OR Prion-Krankheiten D