Franceschini A et al. 2017, High diagnostic value of second generation CSF RT-QuIC across the wide spectrum of CJD prions (Sci Rep 7:10655, PMID 28878311, doi 10.1038/s41598-017-10922-w)

This open access paper from the University of Bologna group (lead author Franceschini, senior author Piero Parchi, with Andrew Hughson and Byron Caughey of NIAID Rocky Mountain Laboratories among the co-authors) compared the first generation (PQ-CSF) and second generation (IQ-CSF) CSF RT-QuIC tests, and then measured how IQ-CSF performs across the range of human prion disease types. It used CSF from 239 people with definite or probable prion disease and 100 with a definite non-prion diagnosis. IQ-CSF found prion seeding activity in about 80 percent of CSF samples that PQ-CSF had called negative, with no loss of specificity, and the authors argued for using it in clinical practice. Sensitivity was high for most sporadic and genetic CJD but lower for two rarer sporadic subtypes and low for variant CJD, GSS and FFI. The record gives aggregate results only; this entry holds no patient-level information. Information only, not medical advice.

Key facts

  • The citation as queued is correct: Franceschini A and 10 co-authors, Scientific Reports 2017, volume 7, article 10655, PMID 28878311, PMC5587608, doi 10.1038/s41598-017-10922-w; first published 6 September 2017 and licensed CC BY.
  • The study set was 239 prion disease CSF samples (definite or probable) and 100 controls with a definite alternative diagnosis such as Alzheimer disease, encephalitis or vascular dementia.
  • The head-to-head comparison used 163 prion disease cases and the 100 controls, and prion samples were largely chosen because earlier PQ-CSF results were negative or only partly positive (93 samples), so it was a retrospective and enriched comparison.
  • Specificity did not differ between the two tests, and none of the 100 non-prion controls was positive by IQ-CSF.
  • Of 58 CJD samples that were negative by PQ-CSF, 47 (about 81 percent) were positive by IQ-CSF; of the 11 that stayed negative, 4 had notable blood contamination.
  • In a clinical-setting series of 187 unselected cases with definite diagnoses (submitted January 2011 to March 2017), IQ-CSF was positive in 141 of 145 CJD cases (sensitivity 97.2 percent), with positive predictive value 100 percent and negative predictive value 91.3 percent.
  • By subtype, IQ-CSF sensitivity was 93.0 percent for sporadic MM1, 100 percent for VV2, 92.3 percent for MV2K, but 66.7 percent for MM2C (6 of 9) and 75 percent for MM2T (3 of 4); the genetic E200K and V210I groups were 20 of 20 and 10 of 10.
  • Detection was weak outside sporadic CJD for variant CJD (1 of 4), GSS P102L (1 of 3) and FFI (0 of 2), which the abstract calls low sensitivity in those conditions.
  • Samples came mostly from the Bologna neuropathology laboratory (282), with 50 from the Besta Neurological Institute in Milan and 7 from the UK National CJD Research and Surveillance Unit in Edinburgh.
  • Funding named in the paper: an Italian Ministry of Health grant and the Gino Galletti Foundation (to Parchi) and the NIAID Intramural Research Program (to Caughey); no competing interests were declared.

Timeline

  1. 2011Start of the clinical-setting submission window analysed for IQ-CSF performance (window ran to March 2017).
  2. 2017End of the clinical-setting submission window.
  3. 2017Paper published online in Scientific Reports on 6 September, PMID 28878311.

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Last checked 1 November 2026

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