TERI-DYNAMIC: Exploring the Impact of Teriflunomide on Immune Cell Population Size, Receptor Repertoire, and Function in Patients With RRMS (P5.282)
Bibliographic record
Abstract
Objective: To explore the immunomodulatory effects of teriflunomide on lymphocyte subsets, repertoire, and function in patients with relapsing-remitting MS (RRMS). Background: Teriflunomide, an immunomodulator approved for patients with relapsing forms of MS, specifically inhibits proliferation of activated lymphocytes. The TERI-DYNAMIC study (NCT01863888) characterized the immunomodulatory effects of teriflunomide treatment on lymphocyte subsets in patients with RRMS. Design/Methods: Patients with RRMS received once-daily oral teriflunomide 14 mg for 24 weeks. Peripheral blood mononuclear cells were isolated at baseline and Weeks 12 and 24. Lymphocyte subsets, including B cells, T cells, and T-cell subpopulations, were analyzed by flow cytometry. Changes in absolute numbers and the diversity of the CD4+ T-cell receptor repertoire were evaluated by deep sequencing. T-cell function was assessed by ex vivo proliferation and cytokine secretion assays. Results: As expected, teriflunomide treatment for 24 weeks significantly reduced absolute numbers and frequencies of lymphocytes and CD19+ B cells in patients with RRMS (n=38). However, within the CD4+ T-cell population, teriflunomide treatment resulted in a selective decrease in Th1 cells compared with Th17 cell proportions, whereas the percentage of inducible Tregs was increased. With regard to the CD4+ T-cell receptor repertoire, teriflunomide treatment for 24 weeks resulted in a significant reduction of overall clonal diversity reflected by a decrease in the total number of unique clones and a reduction in entropy. Functionally, T cells from patients treated with teriflunomide mounted appropriate proliferative and cytokine responses ex vivo. Conclusions: In patients with RRMS, teriflunomide exerted selective effects on different CD4+ T-cell subsets, while ex vivo T-cell function was maintained, supporting the specific immunomodulatory mechanism of action of teriflunomide. This indicates that teriflunomide treatment results in a correction of an enhanced clonal diversity of the CD4+ T-cell repertoire found in patients with RRMS. Study supported by: Genzyme, a Sanofi company.
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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) | 0.000 | 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) | 0.000 | 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".