Evidence map›Paper›PMID 30937539›Full record

ArticlePharmaceutical research2019

How Full-Length FVIII Benefits from Its Heterogeneity - Insights into the Role of the B-Domain.

Julia Anzengruber, Martin Feichtinger, Philipp Bärnthaler, Norbert Haider, Josenato Ilas, Nina Pruckner, Karima Benamara, Friedrich Scheiflinger, Birgit M Reipert, Mantas Malisauskas

Open access · hybridAbstract read
In one paragraph

Article in Pharmaceutical research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.7field-weighted citation impact, top 29% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Julia AnzengruberResearch & Development, Baxalta Innovations GmbH, a Takeda company, Vienna, Austria. julia.anzengruber@takeda.com.
Martin FeichtingerTechnical Operations, Baxalta Innovations GmbH, a Takeda company, Vienna, Austria.
Philipp BärnthalerTechnical Operations, Baxalta Innovations GmbH, a Takeda company, Vienna, Austria.
Norbert HaiderTechnical Operations, Baxalta Innovations GmbH, a Takeda company, Vienna, Austria.
Josenato IlasResearch & Development, Baxalta Innovations GmbH, a Takeda company, Vienna, Austria.
Nina PrucknerTechnical Operations, Baxalta Innovations GmbH, a Takeda company, Vienna, Austria.
Karima BenamaraResearch & Development, Baxalta Innovations GmbH, a Takeda company, Vienna, Austria.
Friedrich ScheiflingerResearch & Development, Baxalta Innovations GmbH, a Takeda company, Vienna, Austria.
Birgit M ReipertResearch & Development, Baxalta Innovations GmbH, a Takeda company, Vienna, Austria.
Mantas MalisauskasResearch & Development, Baxalta Innovations GmbH, a Takeda company, Vienna, Austria.
Takeda (Austria) · AT

Funding

Baxalta Innovations GmbH, a Takeda company, Vienna, Austria not applicable
6 · The paper itself

Abstract

purposeTo explore how the natural heterogeneity of human coagulation factor VIII (FVIII) and the processing of its B-domain specifically modulate protein aggregation.

methodsRecombinant FVIII (rFVIII) molecular species containing 70% or 20% B-domain, and B-domain-deleted rFVIII (BDD-rFVIII), were separated from full-length recombinant FVIII (FL-rFVIII). Purified human plasma-derived FVIII (pdFVIII) was used as a comparator. Heterogeneity and aggregation of the various rFVIII molecular species, FL-rFVIII and pdFVIII were analysed by SDS-PAGE, dynamic light scattering, high-performance size-exclusion chromatography and flow cytometry-based particle analysis.

resultsFL-rFVIII and pdFVIII were heterogeneous in nature and demonstrated similar resistance to aggregation under physical stress. Differences were observed between these and among rFVIII molecular species. FVIII molecular species exhibited diverging aggregation pathways dependent on B-domain content. The propensity to form aggregates increased with decreasing proportions of B-domain, whereas the opposite was observed for oligomer formation. Development of cross-β sheet-containing aggregates in BDD-rFVIII induced effective homologous seeding and faster aggregation. Naturally heterogeneous FL-rFVIII and pdFVIII displayed the lowest propensity to aggregate in all experiments.

conclusionsThese results demonstrate that pdFVIII and FL-rFVIII have similar levels of molecular heterogeneity, and suggest that heterogeneity and the B-domain are involved in stabilising FVIII by modulating its aggregation pathway.

Indexed as

Chromatography, High Pressure LiquidElectrophoresis, Polyacrylamide GelFactor VIIIHumansMass SpectrometryPeptide FragmentsProtein AggregatesProtein StabilityProtein Structural ElementsRecombinant ProteinsB-domain-deleted factor VIIIFactor VIIIPeptide FragmentsProtein AggregatesRecombinant Proteinsblood proteinsfactor VIIIhaemophilia Aprotein aggregatesprotein stability

Identifiers

PMID30937539
PMCPMC6443606
OpenAlexW2929015490

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.