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 24 January 2018

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News

New sensitive assessment method for detection of vCJD

A new sensitive method for the detection of disease-related prion protein in variant Creutzfeldt Jakob disease (vCJD) is described in this week's issue of the Lancet.

News image

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The new technique enables the detection of prion protein in peripheral tissue, suggesting the need for new models of risk-management to prevent the spread of vCJD.

vCJD has a pattern of disease progression distinct from other forms of human prion disease.

Disease-related prion protein (PrPSc) is readily detectable in lymphoid tissues. However, quantifying the risk of secondary infection, and the targeting of risk-reduction strategies, is limited. This is due to the lack of knowledge about the relative prion concentrations in these and other peripheral tissues, the unknown prevalence of preclinical vCJD, and a transmission barrier that limits the sensitivity of biological assessment.

John Collinge and colleagues from the MRC Prion Unit, Imperial College School of Medicine, London, England, used high-sensitivity assessment to identify PrPSc distribution in a range of vCJD tissues.

Tissues were obtained from four patients at post-mortem, who had neuropathologically confirmed vCJD, and from individuals without neurological disease.

Highly sensitive analysis detected PrPSc in peripheral tissue at concentrations 104- to105-fold lower than those reported in the brain.

Tonsil, spleen, and lymph node were positive for PrPSc at concentrations in the range of 0.1-15% of those found in brain. The highest concentrations were consistently seen in tonsil.

vCJD prion proteins found in tonsil, spleen, and rectum, but not appendix.
The Lancet

PrPSc was readily detected in the retina and optic nerve of vCJD eye, at levels of 2·5% and 25%, respectively, of those found in brain.

Other peripheral tissues studied were negative for PrPSc, with the exception of low concentrations in the rectum, adrenal gland, and thymus from a single patient with vCJD.

vCJD appendix and blood were found to be negative for PrPSc.

John Collinge comments, "We have developed a highly sensitive immunoblot method for detection of PrPSc in vCJD tissues. It can be used to provide an upper limit on PrPSc concentrations in peripheral tissues, including blood, to inform risk-assessment models.

"Rectal and other gastrointestinal tissue should be further investigated to assess risk of iatrogenic transmission via biopsy instruments.

"Ophthalmic surgical instruments used in procedures involving optic nerve and the posterior segment of the eye, in particular the retina, might represent a potential risk for iatrogenic transmission of vCJD.

"Tonsil is the tissue of choice for diagnostic biopsy, and for population screening of surgical tissues, to assess prevalence of preclinical vCJD infection within the UK and other populations", he concludes.

In an accompanying Commentary, David Bolton from New York State Institute for Basic Research in Mental Retardation and Developmental Disabilities, USA, states that Collinge and colleagues' results suggest that vCJD prions may be confined primarily to tissues of the central nervous and lymphoid systems. However, he adds that many more samples, tissues, and patients need to be examined.

Lancet 2001; 358 (9277): 164, 171, 208
20 July 2001

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