#604 Effect of felzartamab anti-CD38 treatment on the molecular phenotype of antibody-mediated rejection in kidney transplant biopsies
Bibliographic record
Abstract
Abstract Background and Aims A recent randomized controlled trial demonstrated that treatment with CD38 monoclonal antibody felzartamab suppressed antibody-mediated rejection (ABMR) in kidney transplant patients but with recurrence post-treatment in some patients. Method This study examined the molecular effects of 6-months felzartamab treatment on biopsies from the trial using genome-wide microarray analysis, comparing pre-treatment, end-of-treatment (24 week) and post-treatment (week 52) biopsies from 10 felzartamab and 10 placebo patients. Results Felzartamab reduced molecular ABMR activity scores in all 9 patients with baseline ABMR activity, selectively suppressing interferon gamma (IFNG)-inducible and natural killer (NK) cell transcripts, with minimal effect on ABMR-induced endothelial transcripts and no effect on T cell transcripts. Suppression was often incomplete when ABMR activity was intense, and molecular recurrence was nearly universal by week 52. In genome-wide transcriptome analysis, felzartamab impacted 58 genes between baseline and week 24. Ten of the top 20 differentially expressed genes were decreased, including those associated with ABMR activity. Functional enrichment analysis confirmed the suppression of 12 ABMR-related pathways, reflecting downregulation of NK- and IFNG-induced genes. Of the top 20 differentially expressed genes, 10 were increased. These genes likely represented normal parenchymal genes previously suppressed by ABMR activity, all of which decreased after therapy as ABMR activity returned by week 52. Felzartamab suppressed both IFNG-inducible and NK-expressed ABMR activity genes. From baseline to week 52, felzartamab affected 166 genes. 17 of the top 20 genes were injury-inducible and decreased by week 52, indicating lasting recovery from ABMR-related parenchymal injury after 24 weeks of therapy. Conclusion Felzartamab selectively suppressed IFNG-inducible and NK cell transcripts, offering parenchymal benefits and potentially slowing progression to kidney failure despite near-universal molecular recurrence by week 52.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.004 | 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 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".