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Record W3203750859 · doi:10.1002/jha2.304

Mechanism of increased efficacy of recombinant Fc‐μTP‐L309C compared to IVIg to ameliorate mouse immune thrombocytopenia

2021· article· en· W3203750859 on OpenAlexaff
Bonnie J.B. Lewis, Beth Binnington, Megan Blacquiere, Rolf Spirig, Fabian Käsermann, Donald R. Branch

Bibliographic record

VenueeJHaem · 2021
Typearticle
Languageen
FieldMedicine
TopicMonoclonal and Polyclonal Antibodies Research
Canadian institutionsUniversity of Toronto
Fundersnot available
KeywordsAntibodyImmune systemRecombinant DNAPhagocytosisImmunologyImmune thrombocytopeniaReceptorMonocyteIn vitroPlateletFc receptorCellMedicineChemistryInternal medicineBiochemistry

Abstract

fetched live from OpenAlex

Abstract Recombinant Fc‐μTP‐L309C is more efficacious than intravenous immunoglobulin (IVIg) at ameliorating antibody‐mediated autoimmune diseases through its effects on Fcγ receptors (FcγRs). Fc‐μTP‐L309C inhibited in‐vitro FcγR‐mediated phagocytosis 10 4 /10 5 ‐fold better than IVIg. Fc‐μTP‐L309C, given subcutaneously, recovered platelet counts in an immune thrombocytopenia (ITP) mouse model to a higher degree than IVIg at a 10‐fold lower dose. We show, using confocal microscopy, that Fc‐μTP‐L309C binds to monocyte‐macrophages and is rapidly internalized, whereas, IVIg remains on the cell surface. Western blotting showed that internalized FcγRIII is degraded through a lysosomal pathway, and this reduction of cell surface FcγRIII is likely responsible for the increased efficacy to ameliorate ITP.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.043
Threshold uncertainty score0.904

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.044
GPT teacher head0.336
Teacher spread0.292 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations2
Published2021
Admission routes1
Has abstractyes

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