406.2: Graft protein shows a distinct signature in donor-specific antibody positive kidney transplant recipients with antibody-mediated rejection.
Bibliographic record
Abstract
Introduction: While transplantation is the best treatment for end-stage kidney disease, 50% of grafts fail within 10 years, due mainly to antibody-mediated rejection (ABMR) driven by recipient donor-specific antibodies (DSA). Better strategies are needed to mitigate ABMR, as up to 60% of DSA+ transplant patients do not develop rejection and those with chronic ABMR lack effective treatments. We aim to identify factors regulating kidney protein expression in DSA+ patients with and without rejection.Method: Laser capture microdissection was used to extract glomeruli and tubulointerstitium from formalin-fixed paraffin embedded for-cause kidney biopsies from DSA+ kidney transplant recipients with no rejection (NR, n=45), acute ABMR (aABMR, n=25) and chronic ABMR (cABMR, n=25). Proteins from these tissues were subjected to liquid chromatography mass spectrometry (Q-Exactive HFX) and protein identification was performed using MaxQuant. Perseus software was used to determine significant differential expression within each kidney compartment (ANOVA p<0.05, Tukey post-hoc test q<0.05), and the pathDIP database was used to assess pathway enrichment (FDR q<0.05). Results: 61 tubulointerstitial and 150 glomerular proteins were significantly differentially expressed between DSA+ patients with NR, aABMR or cABMR (Fig. 1). Patients with cABMR showed significant upregulation of components of the classical complement pathway in the glomeruli (q=6.1x10-5) and of terminal complement in the tubulointerstitium (q=6.3x10-15), as well as significantly decreased expression of tubulointerstitial proteins linked to mitochondrial metabolism (q=1.8x10-5), compared to all other groups. Patients with aABMR showed upregulation of tubulointerstitial proteins involved in MHC (q=3.7x10-6) and IFNγ (8.6x10-6) signaling, as well as decreased expression of glomerular proteins linked to extracellular matrix organization (q=6.7e-3). Lastly, DSA+ NR patients had a significant upregulation of proteins linked to metabolism (TI, q=1.7e-3) and the citric acid cycle (glom, q=2.1e-3), as well as higher expression of podocyte-specific proteins in the glomeruli, as compared to patients with either AMR subtype. Conclusion: Overall, these results suggest that while acute and chronic ABMR in DSA+ kidney transplant patients both involve concomitant loss of podocyte-specific proteins and metabolic function, the difference between the two ABMR subtypes may stem from the engagement of distinct immune-mediated mechanisms.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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) | 0.003 | 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".