Low‐dose anti‐<scp>CD</scp>3 antibody induces remission of active autoimmune hepatitis in xenoimmunized mice
Bibliographic record
Abstract
BACKGROUND: Some patients with autoimmune hepatitis (AIH), despite appropriate treatment, progress towards cirrhosis and liver failure, requiring transplantation. New biological agents targeting immune cell subtypes have been developed, with better specificity and longer-lasting effects than conventional wide-spectrum immunosuppressive drugs. AIMS: The goal of this study was to evaluate the effectiveness of low dose of αCD3 targeting therapy in a model of type 2 AIH. METHODS: This experimental model is based on xenoimmunization of C57BL/6 mice with DNA coding for human liver autoantigens. Mice with AIH were treated with five daily injections of low dose of αCD3 monoclonal antibody, before disease onset (5.5 months post-xenoimmunization) or during AIH (7 months post-xenoimmunization). Along with serum aminotransferases, autoantibody levels and end-point liver histology, spleen and liver-infiltrating lymphocytes were phenotyped by flow cytometry and immune response measured by lymphoproliferative assays. RESULTS: Before onset of AIH, treatment prevented the development of liver inflammation and tissue injury. During active AIH, low dose of αCD3 antibody therapy resulted in a resorption of liver inflammatory infiltrates, normalization of serum aminotransferas levels, reduced autoantibody titres, increased regulatory T cells and lowered proliferation of autoreactive liver lymphocytes. CONCLUSIONS: We report that low dose αCD3 antibody administration is an effective treatment for AIH in an experimental model of type 2 AIH. These data suggest that αCD3 antibody therapy could be tested in clinical trials as a rescue therapy for patients with uncontrolled AIH.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
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 teacher head, 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".