Phenotypic and Functional Analysis of Immune Cell Subsets in Pediatric-onset Multiple Sclerosis (MS): Towards Definition of Earliest Disease Mechanisms (P2.236)
Bibliographic record
Abstract
OBJECTIVE: To characterize peripheral immune abnormalities in the earliest stages of MS. BACKGROUND: Substantial efforts have been invested to implicate distinct immune-cell subsets in MS pathophysiology. Though a number of aberrant immune-profiles or responses have been reported in adult-onset MS studies, an ongoing challenge has been to distinguish abnormalities that may develop as a consequence of established disease, from those directly involved in the CNS inflammatory injury of MS. Studying acquired pediatric-onset demyelination offers a unique window into early disease mechanisms given the narrower window between biological- and clinical-disease onset. METHODS: We developed 17 multiparametric flow-cytometry panels capturing both phenotypic and functional response-profiles of multiple immune cell (T and B-lymphocyte, myeloid, NK cell) subsets of putative interest, within both resting and activated peripheral-blood mononuclear cells (PBMC). Assay development included adaptation and validation for use with cryopreserved PBMC obtained using our strict standard operating procedures. We applied the flow-cytometry panels to cryopreserved PBMC obtained from children at time of their initial presentation with acquired demyelinating syndromes (ADS), as part of our prospective Canadian Pediatric Demyelinating Disease Study. Results were compared between children who, in prospective follow-up, were ascertained to have either MS (ADS-MS) or monophasic ADS (ADS-Mono). PBMC from age- and sex-matched healthy controls (HC) were analysed in parallel. RESULTS: A sequential cohort of 21 children examined to date demonstrates that, compared to both HC children and children with ADS-Mono, children with MS harbour significantly higher proportions of circulating CD4+CCR2+CCR5+ T cells (p = 0.0341) and CD8+CD161high mucosal associated invariant T (MAIT) cells (p = 0.0211). These two T-cell subsets were also the highest producers of both IL-17 (p = 0.0186) and IFNγ (p = 0.0043). CONCLUSION: Our findings selectively implicate CD4+CCR2+CCR5+ and CD8+CD161high MAIT T cell subsests in early pediatric-onset MS pathophysiology, but not in pediatric monophasic CNS inflammatory conditions.
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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) | 0.000 | 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".