Contribution of B Cells and Antibody to Cardiac Allograft Vasculopathy
Bibliographic record
Abstract
BACKGROUND: The aim of this study was to determine the role of alloantibody in the development of cardiac allograft vasculopathy (AV). AV is the main pathologic indicator of chronic cardiac graft rejection resulting in graft loss at 10 years posttransplant. In AV, a neointimal lesion forms resulting in luminal occlusion and damage to the transplanted organ. AV is T-cell mediated, but the role played by B cells and antibody in AV development has been controversial. No studies have been conducted in the presence of a clinically relevant immunosuppressant. In our study, we use cyclosporin A, a calcineurin inhibitor. METHODS: Two models of B-cell deficiency were used as recipients of a C3H/HeJ abdominal aortic graft; grafts were harvested at 8 weeks. T- and B-cell immunodeficient mice (RAG1-/-) received passively transferred anti-C3H antibody, raised in B6 mice. Cyclosporin A was administered daily to both control and experimental groups. Alpha-actin staining was used to identify myofibroblasts in the neointima. RESULTS: Lesions in B-cell-deficient B6 mice were not significantly different in size from those of control mice. Lesions in both B-cell-deficient and wild-type mice showed similar levels of alpha-actin positivity. Passive transfer of antibody to RAG1-/- mice resulted in small, alpha-actin-positive lesions. CONCLUSIONS: B cells are not required for the development of AV, but the presence of an alloantibody can contribute to AV. We hypothesize that the alloantibody mediates AV by initiating complement-mediated killing of smooth muscle cells, based on an in vitro work. Of interest, we found that the neointimal lesions of B-cell-deficient mice and mice that received antibody showed the presence of alpha-actin in myofibroblasts.
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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".