Terminal Complement Proteins Dominate Chronic Active Antibody-Mediated Rejection
Bibliographic record
Abstract
Background: Transplantation is the best treatment for end-stage kidney disease, but many grafts fail due to antibody mediated rejection (AMR). Diagnostic criteria includes graft injury, C4d deposition on the endothelium, and circulating donor-specific antibodies (DSA). AMR is stratified into aucte (aAMR) or chronic-active (caAMR), by basement membrane doubling in caAMR. Notably, 50% of patients showing microvascular inflammation consistent with AMR don't have DSA. Methods: Laser capture microdissection was used to separate tubulointerstitium (TI) and glomeruli of biopsies from 83 DSA+ and DSA- patients with aAMR or caAMR, followed by unbiased proteomic analysis on a Q-Exactive HFX mass spectrometer. Results: Complement proteins were amongst the most significantly differentially expressed proteins in both compartments (p<0.05). C6, C8B, and C8G were increased in TI of DSA+AMR biopsies compared to DSA-AMR biopsies. Terminal complement proteins were increased in caAMR compared to aAMR. In glomeruli, complement proteins were increased in caAMR. Preliminary imaging mass cytometry shows C5a expression in the basement membranes of 2 biopsies with caAMR, and activated C5b-9 co-stained with IgG. Conclusion: Increased complement expression and C5a in the basement membranes suggests complement involvement in caAMR.
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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) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".