Frontzek et al. 2020, Autoantibodies against the prion protein in individuals with PRNP mutations (Neurology)

This Neurology paper reports a case-control study from the University of Zurich group around Adriano Aguzzi, run as the THAUTAN-MC study (ClinicalTrials.gov NCT02837705). It asked whether people with genetic prion disease variants make natural antibodies against normal prion protein that could explain late disease onset and be copied as a treatment. Blood from 124 variant carriers and 78 controls from affected families was tested; antibody levels did not differ by variant status or clinical state, so the answer was negative. It was published online on 25 February 2020 and in print on 6 October 2020. All findings here are aggregate group results; no individual is described.

Key facts

  • Citation: Neurology 2020;95(14):e2028-e2037, DOI 10.1212/WNL.0000000000009183, PMID 32098855, PMCID PMC7682844; twenty named authors plus the THAUTAN-MC Study Group, with Aguzzi as corresponding author.
  • The paper is labelled a Null Hypothesis article, meaning it reports a negative result.
  • Design: case-control; 124 samples from carriers of pathogenic PRNP variants and 78 from controls with a family history but no disease-associated variant. A tool summary of the full text says 202 of 241 sampled individuals were selected for the unmatched analysis.
  • Method: ELISA for IgG1 to IgG4 against wild-type human prion protein, with log-transformed titers, multivariable regression (age and plasma versus serum as covariates) and a matched sensitivity analysis on age, sex and sample type.
  • Result: antibody reactivity occurred in a subset of both carriers and controls, and titers were not affected by variant status or by symptomatic versus asymptomatic state, also in matched subsets.
  • Titers rose or fell with age and sample type, but not with sex, codon 129 genotype or documented autoimmune history; a small repeat-sample subset showed no group difference in yearly change.
  • Conclusion quoted from the abstract in substance: pathogenic PRNP variants do not notably stimulate antibody-mediated anti-PrPC immunity, and such antibodies are not tied to disease onset; their presence in the wider population suggests high natural titers are well tolerated.
  • Stated limits: only wild-type full-length PrPC was used as antigen, so protective antibodies of other kinds are not excluded; some subgroups were very small and many analyses were post hoc; participants came through patient organizations and reference centers, so selection bias is possible.
  • Funding listed includes EPSRC, BBSRC, ERC, the Frances and Augustus Newman Foundation, NIH (R01 NS103848), CDC and Prion Alliance (for sample collection at one US site); the authors state the funders had no role in the work.
  • Ethics approval came from the Cantonal Ethics Committee of Zurich and written consent was obtained; the study is registered as NCT02837705.
  • Europe PMC counted 14 citing records at the time of the fetch, and links a preprint (PPR95036).

Timeline

  1. 2016The study was first registered on ClinicalTrials.gov (date taken from the study entity, not from the paper).
  2. 2020Paper published online in Neurology.
  3. 2020Print issue (volume 95, issue 14).

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Last checked 1 November 2026

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