DISTINCT MOLECULAR PROFILES OF REMISSION POST-CD19 CAR-T CELL THERAPY VERSUS STANDARD IMMUNOSUPPRESSION IN SYSTEMIC LUPUS ERYTHEMATOSUS
Bibliographic record
Abstract
O006 / #412 Topic:AS12 - Genetics, Epigenetics, Transcriptomics SCIENTIFIC HYBRID SESSION: CLINICAL TRACK PRESENTATIONS - OUTSTANDING ABSTRACT PRESENTATIONS 23-05-2025 9:00 AM - 10:00 AM Background/Purpose Remission, as defined by the Definition of Remission in SLE (DORIS) criteria, is the primary therapeutic target in systemic lupus erythematosus (SLE). While DORIS remission correlates with the reversal of key pathogenic processes,[1] novel approaches like CD19-targeted chimeric antigen receptor (CAR)-T cell therapy have shown potential to induce durable, drug-free remission. Yet, the molecular characteristics of CAR-T cell-induced remission compared to standard immunosuppression-induced remission remain unclear. Methods To delineate unique molecular profiles of CD19 CAR-T cell therapy-induced remission, we performed a comparative analysis of Reactome pathways. Pseudo-bulk expression profiles were generated from single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) in 7 SLE patients post-lymphodepletion and CAR-T cell infusion. As a comparator, transcriptional profiles from 34 SLE patients in DORIS remission on standard immunosuppression from the PRECISESADS project (1) were analyzed. Functional pathway annotations were derived using the Functional Analysis of Individual Microarray Expression (FAIME) algorithm. Results Of 314 pathways, 22 pathways related to the immune system were significantly differentially regulated, with CAR-T cell-induced remission being associated with a greater suppression of type I interferon, complement activation, and interleukin signaling pathways. Notably, Fc gamma receptor IIIa-mediated IL-10 synthesis and lipid metabolism pathways were selectively upregulated, suggesting enhanced antiinflammatory responses and metabolic rewiring. CD19 CAR-T cell-induced remission was also marked by decreased DNA damage response activation compared to remission on standard immunosuppression. Conclusions Our findings reveal a distinct immune and metabolic landscape associated with CD19 CAR-T cell-induced remission in SLE, supporting the notion of CD19 CAR-T cell-mediated immunological reset.References:[1] Parodis I. Ann Rheum Dis. 2024;83(7):889-900.
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 | 0.000 |
| 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) | 0.001 | 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".