Plasma prion amplification test for variant CJD (EFS blood service with the Paris Brain Institute, 2016)

Key facts

• The assay captures abnormal prion protein from plasma on plasminogen coated beads and then multiplies it by protein misfolding cyclic amplification, reaching femtomolar detection; the readout is an immunoassay after amplification.
• In 256 plasma samples from France and the UK it identified all 18 clinical variant CJD patients, giving sensitivity of 100 percent with a 95 percent confidence interval of 81.5 to 100.
• The reported specificity figures are 99.2 percent analytical (95 percent CI 95.9 to 100) and 100 percent diagnostic (95 percent CI 96.5 to 100), on the samples from people without variant CJD.
• The same run detected prion carriage in two blood donors 1.3 and 2.6 years before their disease began, the first published human evidence that this chemistry can read plasma before symptoms.
• The work was done by the EFS TransDiag laboratory in Montpellier with the Paris Brain Institute prion team, the national CJD surveillance network and the national reference centre for unconventional transmissible agents, INRAE at Jouy-en-Josas and the Edinburgh National CJD Research and Surveillance Unit.
• Funding named on the record includes the UK Department of Health Policy Research Programme with NIHR under grant PRST061400008, the Alliance Biosecure Foundation, Inserm and the Institut de veille sanitaire.
• The uses the developers put forward are telling variant CJD from other forms of CJD, testing how well manufacturing steps remove or inactivate prions, studying how prions distribute across blood fractions, and in the long run population measurement if the method can be automated.
• A separate amplification blood test for variant CJD from the Mitchell Center at UTHealth Houston, with Santiago, Milan and Edinburgh groups, was published in the same December 2016 issue of the journal, reporting 100 percent sensitivity and specificity on 14 variant CJD cases and 153 controls; the two efforts are independent and share no authors.
• In 2018 the same Montpellier group moved the method to spinal fluid and reported 40 of 41 clinical variant CJD samples positive and none of 57 non-variant samples positive, while stating the work needs a biosafety level 3 laboratory and highly experienced staff and making no claim of a validated clinical test.
• Sporadic CJD has resisted this chemistry: a 2021 paper from the same laboratory found that amplification of sporadic prions depends strongly on both seed and substrate, and reports no blood or plasma result for sporadic disease.
• Nothing opened shows the test entering donor screening, a clinical service or a regulatory process; the UK route for judging such tests runs through the NIBSC CJD Resource Centre, which sends identical blinded panels to developer groups and has judged at least one candidate unsuitable for donor screening.
• European policy has moved without a test: a 2024 European Blood Alliance consensus, coauthored by the assay's first author and a second EFS author (the full text gives only EFS affiliations, so this author's role as national medical director is not confirmed), judges the residual transfusion risk minimal and discusses geographic deferrals rather than any screening assay, while a 2021 ECDC assessment had said the residual risk could not be judged with confidence in the absence of a reliable blood test.

Timeline

1. 2015The ANR project UnmaskingBloodPrions starts, 655,720 euro over 36 months, with EFS TransDiag as a partner alongside CEA SEPIA, Inserm UMR ICM, Hospices Civils de Lyon and INRA Toulouse, aiming at tools to find prions in blood.
2. 2016The plasma assay is published in Science Translational Medicine, in the same issue as the Houston blood amplification paper.
3. 2016Electronic publication date recorded by the Edinburgh repository.
4. 2016The Paris Brain Institute announces the test publicly and names the partner bodies and the intended uses.
5. 2017Trade coverage reports both December 2016 assays together and notes that both teams called for more research.
6. 2018The Montpellier group publishes the spinal fluid version in Emerging Infectious Diseases, used to tell variant from sporadic CJD in a codon 129 heterozygous case.
7. 2021ECDC assessment of variant CJD risk from UK blood and plasma products states that without a reliable blood test the residual risk cannot be judged with confidence.
8. 2024European Blood Alliance consensus on transfusion transmitted variant CJD is published, naming no screening assay.
9. 2026The TransDiag laboratory publishes amplification work on tau, evidence the group remains active but that its recent output has moved away from blood prion detection.