Novel screening test may benefit variant Creutzfeldt-Jakob Disease patients

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1. A new assay for detection of variant Creutzfeldt-Jakob Disease (vCJD) has 100% specificity, making it an ideal screening test for vCJD in prion-exposed populations.

2. The estimated sensitivity of the assay for vCJD-infected patient blood samples is around 70%. 

Evidence Rating Level: 1 (Excellent) 

Study Rundown: Prion diseases represent a class of fatal transmittable neurodegenerative diseases. A variant from of CJD (vCJD) is acquired through exposure to Bovine Spongiform Encephalopathy, a cattle prion disease. 750,000 of the 3 million cattle in the UK affected with BSE were used for human consumption, raising concerns over widespread exposure. The estimated sensitivity of the assay (70%), extremely high specificity (100%), and no cross-reactivity and false-positives in samples from patients with non-prion neurodegenerative disease make it an ideal tool for screening and diagnosis of vCJD.

The strengths of the study include rigorous validation of a serum detection assay for vCJD using large samples, including a subset of samples with potential cross-reactivity (patients with non-prion neurodegenerative disorders). The cutoffs selected in the study achieved perfect specificity while still retaining a reasonable sensitivity. It is unclear from the current study whether this new assay will be able to detect vCJD in subclinical carriers or patients early in their disease progressions, as these sub-groups may even have lower levels of abnormal proteins in their blood. Further work with larger samples of high-risk will be needed to provide estimates of vCJD blood prevalence, and hence key decisions regarding vCJD screening.

Click to read the study, published today in JAMA Neurology

Relevant Reading: Identification of Misfolded Proteins in Body Fluids for the diagnosis of Prion Diseases

In-Depth [retrospective cross-sectional diagnostic study]: This study determined the diagnostic accuracy of a new serum assay for detecting vCJD using anonymous samples from national blood collection and prion disease centers in the United Kingdom (UK) and United States (US). The study samples included 5,000 healthy US blood donors, 200 healthy UK donors, 352 patients with non-prion neurodegenerative disease, 105 patients with a likely prion disease diagnosis, and 10 patients with confirmed vCJD.

Of the 5,000 US samples, no samples tested positive, resulting in specificity of 100% (95% CI, 99.93–100%). A similarly high specificity was confirmed in a UK “Normals” (100%, 95% CI, 98.2–100%) and in patients with non-prion neurodegenerative diseases (100%, 95% CI, 98.9–100%). In both normal cohorts, 1.8% of the samples were reactive after the first test, and non-reactive after a second test. This suggests a theoretical false-positive (repeat-reactive) rate of 1 in 3,000 normal samples (99.97% specificity). In the sub-group of patients in which a prion disease was likely, 2 of 105 tested positive for sporadic CJD. Both these patients had a clinical sCJD diagnosis. A small blinded panel of 5 US normal samples and 10 samples with vCJD achieved a specificity of 100% and sensitivity of 70%.

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