A Mouse Model for ABO-Incompatible Transplantation (ABOi Tx): Study of Antibody-Mediated Rejection (AMR) Following ABOi Heart Tx.
Bibliographic record
Abstract
Purpose: The ABO blood group system is generally a barrier to safe organ Tx between incompatible donors and recipients. However, in infants ABOi heart Tx (HTx) can be performed safely as anti-blood group antibody levels are low or absent. Following ABOi HTx, immune tolerance develops to the donor A/B antigen(s), by mechanisms not well understood. Mice do not normally express ABO antigens, therefore we developed transgenic mice (A-Tg, C57BL/6 [B6] background) expressing human A-antigen on vascular endothelium. ‘A into O' ABOi HTx can be approximated using A-Tg mice as donors and wild-type (WT) B6 mice as recipients. Herein, we investigated AMR following Tx of A-Tg hearts into WT mice. We hypothesize that A-Tg grafts will undergo AMR in WT recipients with circulating anti-A antibodies. Methods: WT B6 mice (6-12 weeks old) were induced (sensitized) to produce anti-A antibodies by subcutaneous injection of human A red blood cells. Serum anti-A antibody titres were assessed by hemagglutination assays. Sensitized WT recipients received a heart transplant from an A-Tg (n=15) or WT (n=6) donor, and graft pulsation was monitored by palpation. Grafts were harvested following cessation of beating or at 7-14 days post-transplant (median 13 days); AMR was assessed by histology. Results: Sensitization resulted in high anti-A Ab titres (median 1:512). There was morphological evidence of AMR in 6 of 15 of the A-Tg heart grafts transplanted into WT recipients; of these, 2 ceased beating within 24 hours post-transplant and showed morphological signs of hyperacute rejection. Grafts with morphological features of AMR also showed evidence of C4d deposition. No WT heart grafts showed evidence of AMR. Conclusion: These findings indicate that incompatible A-Tg heart grafts can undergo AMR following Tx into WT mice with high anti-A antibody titre; however not all A-Tg grafts showed morphological features of AMR within the study period. Ongoing studies are addressing AMR beyond 14 days of Tx. This model will be a valuable resource for studies related both to rejection and tolerance in the setting of ABOi transplantation.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".