Peripheral immune cell profiles in fingolimod treated multiple sclerosis patients following short term drug interruption (P1.155)
Bibliographic record
Abstract
Objective- To evaluate the reconstitution of the peripheral immune cell repertoire (regulatory and effector CD4 and CD8 T-cell subsets as well as RTEs) following a temporary (10-14 days) interruption in treatment in patients treated with fingolimod. Background- The effects of fingolimod are attributed to sequestration of CCR7+ cell subsets within lymph nodes. It also prevents newly generated T-cells, recent thymic emigrants (RTEs), from exiting the thymus. Fingolimod may alter immune regulatory and effector function by direct signaling mechanisms. Methods- Peripheral blood was obtained both while on treatment and 10 to 14 days following treatment interruption. Total lymphocyte counts (TLCs), and CD4/CD8 counts were measured by a clinical laboratory. T cell subsets were investigated in cryopreserved peripheral blood mononuclear cells (PBMCs) using multicolor flow cytometry. Results- In 3 patients treated for <5 years, TLCs increased on average 0.077 X 109 cells/L, to 0.63 x109 cells/L. Increases in CD4+ and CD8+ T-cell subsets consisted of: naïve (CD45RA+CCR7+) CD4 T cells - mean 30.04 cells/ul and CD8 cells - 18.54 cells/ul; TCM (CD45RA-CCR7+) CD4 - mean 50.97 cells/ul and CD8 cells - 13.6 cells/ul; Treg (CD4+CD25+Foxp3+) - mean 7.21 cells/ul; and RTE (CD31+CD45RA+) - mean 16.02 cells/ul. Mean TLCs in a cohort treated for 10 years (n=5) was 0.37x109 cells/L compared to 0.51x109 for our overall cohort of patients treated for <5 years (n=5). Mean OFF-TX values were 0.57x109 cells/L and 0.81x109 respectively, an increase from ON-TX values of 50.44[percnt] and 66.47[percnt]. CD4:CD8 ratios increased by 48.55[percnt] and 54.94[percnt] respectively. Conclusions - Although conducted at a time of partial reconstitution, our data does not suggest a selective change in T cell effector or regulatory profiles in patients on short-term fingolimod treatment. Longer-term therapy exceeding the life span of naïve CD4 and CD8 T cells (5-8years) may have more persistent effects.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 | 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".