PB0143 Induced B Cell Tolerance in Hemophilia A Mice is Destroyed by Infections
Bibliographic record
Abstract
Background: Haemophilia A is an X-linked bleeding disorder characterized by a deficiency of factor VIII (FVIII).Patients may develop anti-FVIII antibodies, rendering FVIII therapy ineffective.Antibody production can be suppressed by targeting CD32 receptors in B cells using immune complexes.Binding FVIII/anti-FVIII immune complexes (FVIII-ICs) to FcγRIIB leads to phosphorylation of the immune receptor tyrosine-based inhibition motif (ITIM) tail of FcγRIIB and send inhibitory signals to B cells, thereby inhibiting antibody production.Aims: To evaluate the effect of FVIII-ICs administration on the suppression of antibody production by B cells in a mouse model.Methods: FVIII antibodies were produced by immunization of FVIII KO mice with rFVIII and isolation of plasma containing anti-FVIII antibodies.FVIII-ICs were prepared by incubation of the plasma antibody pool with rFVIII at 1:1 and 1:10 ratios.FVIII KO mice were then injected retro-orbitally with FVIII-ICs, PBS, or rFVIII diluted in naïve plasma once weekly for four weeks (tolerization phase).Next, FVIII was administered retro-orbitally, at a dose of 25 IU/kg once weekly for 4 weeks.Finally, blood samples were collected from all mice and the concentration of anti-FVIII antibodies was determined by ELISA (Figure 1).
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.007 | 0.003 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".