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The Journal of Pathology. Large-scale immunohistochemical examination for lymphoreticular prion protein in tonsil specimens collected in Britain
Large-scale immunohistochemical examination for lymphoreticular prion protein in tonsil specimens collected in Britain (The Journal of Pathology, abstract, edited)
[Source: The Journal of Pathology, full text: <cite cite="http://onlinelibrary.wiley.com/doi/10.1002/path.2767/abstract">Large-scale immunohistochemical examination for lymphoreticular prion protein in tonsil specimens collected in Britain - de Marco - 2010 - The Journal of Pathology - Wiley Online Library</cite>. Abstract, edited.]
Large-scale immunohistochemical examination for lymphoreticular prion protein in tonsil specimens collected in Britain?
1. Mar Fernandez de Marco 1, 2. Jacqueline Linehan 2, 3. O Noel Gill 3, 4. Jonathan P Clewley 3,*, 5. Sebastian Brandner 1,*
Article first published online: 4 OCT 2010
DOI: 10.1002/path.2767
Copyright ? 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Author Information
1. 1 Division of Neuropathology and Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK
2. 2 MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK
3. 3 Centre for Infections, Health Protection Agency, 61 Colindale Avenue, London NW9 5EQ, UK
Email: Jonathan P Clewley (jonathan.clewley@hpa.org.uk), Sebastian Brandner (sebastian.brandner@prion.ucl.ac.uk)
*Correspondence: Jonathan P Clewley, (Regarding the tonsil archive) Centre for Infections, Health Protection Agency, 61 Colindale Avenue, London NW9 5EQ, UK
*Correspondence: Sebastian Brandner, (Regarding the IHC) Division of Neuropathology and Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK
1. ? No conflicts of interest were declared.
Publication History
1. Article first published online: 4 OCT 2010
2. Manuscript Accepted: 10 AUG 2010
3. Manuscript Revised: 22 JUL 2010
4. Manuscript Received: 24 MAY 2010
Funded by * Policy Research Programme in the Department of Health, UK
Abstract
There have been 173 cases of variant Creutzfeldt?Jakob disease (vCJD) in the UK, as of 5 July 2010, as a result of the bovine spongiform encephalopathy epidemic. The number of individuals subclinically infected with vCJD, and thus the eventual number of cases, remains, however, uncertain. In an attempt to address this problem, 63 007 tonsil tissue specimens were previously tested by enzyme immunoassay (EIA) for the presence of disease-related prion protein (PrPres) and found to be negative. To confirm the reliability of this result, all those in the birth cohort most at risk (1961?1985) and a few others, including controls, have now been tested by immunohistochemistry (IHC). Histological slides were prepared from 10 075 anonymized formalin-fixed, paraffin-embedded tissues and examined for PrPres with two anti-prion protein antibodies, ICMS35 and KG9. One specimen showed a single strongly positive follicle with both antibodies, on two slides from adjacent sections. As this specimen was negative when it was further investigated by EIA, IHC, and immunoblotting, it is unclear whether the patient from whom the tonsil came will go on to develop vCJD. If, however, this is the case, then a finding of 1 out of 9160 gives a prevalence of disease-related prion protein in the British population of 109 per million, with a 95% confidence interval (CI) of 3?608 per million, which is not statistically different (exact p = 0.63) from population prevalence estimates based on finding three positives out of 10 278 in a previous IHC study of appendix tissue. If this is not the case, a finding of 0 out of 9160 gives a prevalence of 0?403 per million (95% CI) for the 1961-1985 cohort, which is also not different (exact p = 0.25) from previous population prevalence estimates. Therefore, the results of this work could be summarized as finding, by IHC, no or one vCJD-positive individual.
Copyright ? 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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[Source: The Journal of Pathology, full text: <cite cite="http://onlinelibrary.wiley.com/doi/10.1002/path.2767/abstract">Large-scale immunohistochemical examination for lymphoreticular prion protein in tonsil specimens collected in Britain - de Marco - 2010 - The Journal of Pathology - Wiley Online Library</cite>. Abstract, edited.]
Large-scale immunohistochemical examination for lymphoreticular prion protein in tonsil specimens collected in Britain?
1. Mar Fernandez de Marco 1, 2. Jacqueline Linehan 2, 3. O Noel Gill 3, 4. Jonathan P Clewley 3,*, 5. Sebastian Brandner 1,*
Article first published online: 4 OCT 2010
DOI: 10.1002/path.2767
Copyright ? 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Author Information
1. 1 Division of Neuropathology and Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK
2. 2 MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK
3. 3 Centre for Infections, Health Protection Agency, 61 Colindale Avenue, London NW9 5EQ, UK
Email: Jonathan P Clewley (jonathan.clewley@hpa.org.uk), Sebastian Brandner (sebastian.brandner@prion.ucl.ac.uk)
*Correspondence: Jonathan P Clewley, (Regarding the tonsil archive) Centre for Infections, Health Protection Agency, 61 Colindale Avenue, London NW9 5EQ, UK
*Correspondence: Sebastian Brandner, (Regarding the IHC) Division of Neuropathology and Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK
1. ? No conflicts of interest were declared.
Publication History
1. Article first published online: 4 OCT 2010
2. Manuscript Accepted: 10 AUG 2010
3. Manuscript Revised: 22 JUL 2010
4. Manuscript Received: 24 MAY 2010
Funded by * Policy Research Programme in the Department of Health, UK
Abstract
There have been 173 cases of variant Creutzfeldt?Jakob disease (vCJD) in the UK, as of 5 July 2010, as a result of the bovine spongiform encephalopathy epidemic. The number of individuals subclinically infected with vCJD, and thus the eventual number of cases, remains, however, uncertain. In an attempt to address this problem, 63 007 tonsil tissue specimens were previously tested by enzyme immunoassay (EIA) for the presence of disease-related prion protein (PrPres) and found to be negative. To confirm the reliability of this result, all those in the birth cohort most at risk (1961?1985) and a few others, including controls, have now been tested by immunohistochemistry (IHC). Histological slides were prepared from 10 075 anonymized formalin-fixed, paraffin-embedded tissues and examined for PrPres with two anti-prion protein antibodies, ICMS35 and KG9. One specimen showed a single strongly positive follicle with both antibodies, on two slides from adjacent sections. As this specimen was negative when it was further investigated by EIA, IHC, and immunoblotting, it is unclear whether the patient from whom the tonsil came will go on to develop vCJD. If, however, this is the case, then a finding of 1 out of 9160 gives a prevalence of disease-related prion protein in the British population of 109 per million, with a 95% confidence interval (CI) of 3?608 per million, which is not statistically different (exact p = 0.63) from population prevalence estimates based on finding three positives out of 10 278 in a previous IHC study of appendix tissue. If this is not the case, a finding of 0 out of 9160 gives a prevalence of 0?403 per million (95% CI) for the 1961-1985 cohort, which is also not different (exact p = 0.25) from previous population prevalence estimates. Therefore, the results of this work could be summarized as finding, by IHC, no or one vCJD-positive individual.
Copyright ? 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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