ORIGINAL ARTICLE
Removal of exogenous prion infectivity in leukoreduced red blood cells unit
by a specific filter designed for human transfusion
Nathalie Lescoutra-Etchegaray1,*, Chryslain Sumian2, Audrey Culeux1,
Valérie Durand3, Patrick V. Gurgel4, Jean-Philippe Deslys3, Emmanuel E. Comoy3
Article first published online: 10 OCT 2013
DOI: 10.1111/trf.12420
© 2013 American Association of Blood Banks
Lescoutra-Etchegaray, N., Sumian, C., Culeux, A., Durand, V., Gurgel, P.
V., Deslys, J.-P. and Comoy, E. E. (2013), Removal of exogenous prion
infectivity in leukoreduced red blood cells unit by a specific filter designed
for human transfusion. Transfusion. doi: 10.1111/trf.12420
Author Information 1 Macopharma, Fontenay-aux-Roses, France 2 Macopharma,
Tourcoing, France 3 Institute of Emerging Diseases and Innovative Therapies
(iMETI), Division of Prions and Related Diseases (SEPIA), CEA,
Fontenay-aux-Roses, France 4 ProMetic Biosciences, Raleigh, North Carolina
*Address reprint requests to: Nathalie Lescoutra-Etchegaray, Macopharma, 18
Route du Panorama, Bâtiment 60, 92265 Fontenay-aux-Roses, France; e-mail:
nathalie.lescoutra@macopharma.com.
This work was supported by grants from Agence Nationale de la Recherche
(ANR), Project PRIONSECUR ANR05PRIB02302.
Publication History Article first published online: 10 OCT 2013 Manuscript
Accepted: 12 JUL 2013 Manuscript Revised: 10 JUL 2013 Manuscript Received: 23
APR 2013 Funded by Agence Nationale de la Recherche (ANR). Grant Number:
PRIONSECUR ANR05PRIB02302
Background
Five cases of variant Creutzfeldt-Jakob disease (vCJD) infections were
attributed to infusion of contaminated blood components, turning to real the
interhuman transmissibility of this prion disease from asymptomatic carriers.
Preventive policies rely on exclusion from blood donation and benefit of
leukoreduction initially implemented against leukotropic viruses. In the absence
of available antemortem diagnostic tests, the updated prevalence of silent vCJD
infections (1/2000 in the United Kingdom) urges the necessity to enforce blood
safety with more efficient active measures able to remove the remaining
infectivity.
Study Design and Methods Several affinity resins were demonstrated to
reduce high levels of brain-spiked infectivity from human leukoreduced red blood
cells (L-RBCs). One was integrated in a device adapted to field constraints
(volumes, duration) of human transfusion. We assessed here the ability of the
resulting removal filter, termed P-Capt, to remove infectivity from human L-RBC
units spiked with scrapie-infected hamster brain (≥10,000 infectious units/mL),
through inoculation of hamsters with pre- and post–blood filtration
samples.
Results Incubation periods of recipient animals suggest around a 3-log
removal of brain-derived prion infectivity by filtration through the
P-Capt.
Conclusion On brain-derived spiked infectivity, the P-Capt filter provided
a performance similar to the resin packed in columns used for initial
proof-of-concept studies, suggesting an appropriate scale-up to efficiently
remove infectivity from an individual human blood bag. According to the ability
of resin to completely remove apparent endogenous infectivity from hamster
leukoreduced blood, the implementation of such a filter, now commercially
available, might seriously improve blood safety toward prions.
Sunday, September 29, 2013
Recalls raise questions on safety practices for donated blood CJD TSE PRION
Sent: Monday, October 07, 2013 9:54 PM
Subject: [CJD-L] Coexistence of Distinct Prion Types Enables Conformational
Evolution of Human PrPSc by Competitive Selection
TSS