Naturally occurring antibodies against prion proteins found in humans


Date:
August 17, 2020
Source:
EMBO
Summary:
Antibodies targeting the normal PrP version of the prion protein
have been found in humans selected at random with no history of any
associated transmissible spongiform encephalopathies. Researchers
report on active antibodies against PrP at high levels in a
small proportion of individuals, 21 of 37,894 hospital patients
screened for presence of anti-PrP IgGs, the most common form of
immunoglobulin.



FULL STORY ========================================================================== Antibodies targeting the normal PrP version of the prion protein have
been found in humans selected at random with no history of any associated transmissible spongiform encephalopathies. The significance is that prion proteins can be converted into a disease-causing infectious particle
like PrPSc, an aggregated version or isoform resistant to degradation by protease enzymes. Resulting prion diseases, like other neurodegenerative syndromes such as Alzheimer's disease and Parkinson's disease, are
associated with accumulation of misfolded and aggregated proteins in
the central nervous system. Antibodies against such proteins may be
beneficial and offer potential for therapies against such diseases by
targeting the pathological aggregates for degradation by phagocytic cells.


==========================================================================
In EMBO Molecular Medicine, researchers at the University of Zurich
and Novartis Institutes for BioMedical Research in Switzerland report
on active antibodies against PrP at high levels in a small proportion
of individuals, 21 of 37,894 hospital patients screened for presence of anti-PrP IgGs, the most common form of immunoglobulin. There was strong evidence from lack of any past history of disease among these individuals
that these antibodies were not themselves neurotoxic. That, combined with
the lack of such antibodies among people who do carry disease-causing
mutations in the PRNP gene coding for prion proteins, suggests they
might have cleared unwanted nascent disease prions early in life.

Earlier research had already shown that anti-PrP antibodies are effective
in mice infected with prions and also some human cells, suggesting they
might represent a viable therapeutic strategy. However, it has also been demonstrated that the biological effect of anti-PrP antibodies depends critically on which part, or epitope, of the PrP prion recognized by
the immune system is targeted.

Therefore, the latest work sought to produce a high-resolution map
of neuroprotective epitopes, with the ultimate goal of identifying immunotherapeutics that might be effective, as well as safe by avoiding neurotoxic effects. This was achieved by discovering antibodies that
targeted both the main globular domain (GD) of the prion protein and
its flexible tail (FT). This suggested there was a polyclonal antibody response, offering further evidence for the existence of naturally
occurring antibodies against the prion protein in humans.

The resulting immune response capable of clearing nascent infectious
prions may then operate analogously to immune surveillance for neoplastic
cells that cause cancer. At the very least, generation of antibodies
to the whole set of PrP epitopes provides new tools for studying the
mechanism of neurodegeneration conveyed by prions.


========================================================================== Story Source: Materials provided by EMBO. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Assunta Senatore, Karl Frontzek, Marc Emmenegger, Andra Chincisan,
Marco
Losa, Regina Reimann, Geraldine Horny, Jingjing Guo,
Sylvie Fels, Silvia Sorce, Caihong Zhu, Nathalie George,
Stefan Ewert, Thomas Pietzonka, Simone Hornemann, Adriano
Aguzzi. Protective anti‐prion antibodies in human
immunoglobulin repertoires. EMBO Molecular Medicine, 2020; DOI:
10.15252/emmm.202012739 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200817123043.htm

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