New sensitive assessment method for the detection of vCJD

July 19, 2001

Please note that if you are outside North America, the embargo for LANCET press material is 0001 hours UK Time Friday 20th July.

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. 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 by 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 which limits the sensitivity of biological assessment. John Collinge and colleagues from the MRC Prion Unit, Imperial College School of Medicine, London, UK, aimed to use 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 104-105-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. 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 negative for PrPSc.

John Collinge comments: "We have developed a highly sensitive immunoblot method for detection of PrPSc in vCJD tissues that 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."

In an accompanying Commentary (p 164), David Bolton from New York State Institute for Basic Research in Mental Retardation and Developmental Disabilities, USA, states that Collinge and colleagues' results (like those of a different study by M E Bruce and colleagues about the infectivity of vCJD also reported in a research letter [p 208] in this week's issue of THE LANCET), suggest that vCJD prions may be confined primarily to tissues of the central nervous and lymphoid systems, but adds that many more samples, tissues, and patients need to be examined.
Contact: (NB only available after 1300 H Thursday 19 July, UK time) Professor John Collinge, Prion Disease Group, Department of Neurogenetics, Imperial College of Medicine at St Mary's Hospital, Norfolk Place, LONDON W2 1PG,UK;T) 020 7594 3760; F) 020 7706 7094;E)

Dr David Bolton, Department of Molecular Biology, Staten Island, New York, NY 10314, USA; T) +1 718 494 5187/ 283; F) +1 718 494 5905; E)


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