Innate lymphocytes -ILC2- might be the drivers of T2-high nonatopic asthma in children
Bibliographic record
Abstract
Background: Asthma in children is usually considered a T2-high (T2H) atopic disease, yet the T2H non-atopic and T2-low (T2L) endotypes, seen in adults, have not been well defined in children. Aim: To investigate the expression of innate lymphoid cells-2 (ILC2), IL-4 and IL-5 in the different endotypes of childhood asthma. Methods: In bronchial biopsies of 109 children (61 with, 48 without asthma) undergoing a clinical indicated bronchoscopy, we quantified by immunohistochemistry eosinophils (eos), ILC2, IL-4 and IL-5+ cells and remodelling hallmarks such as thickening of the basement membrane (BM) and epithelial shedding. Results: 45 (73%) children were T2H (eos>23cell/mm2), 16 (27%) T2L. Among T2H children, 23 (51%) were atopic (T2H-A) and 22 (49%) non-atopic (T2H-nA). Eos were similar in T2H-A and T2H-nA [158±127 vs 150±180cell/mm2]. IL-5 was similarly increased in T2H-A and T2H-nA [414±165 and 434±178 vs T2L 268±93 and controls 281±158 cell/mm2;p=0.04] and was related to eos (r=0.51;p=0.005). IL-4 was significantly higher in T2H-A than in T2H-nA [220±164 vs 73±42cell/mm2;p=0.04] and related to IgE (r=0.32;p=0.04) and eos (r=0.59;p=0.004). ILC2 cells were increased in T2H-nA and almost absent in the other groups [41±18 vs T2H-A 9±13, T2L and CTR 5±7cell/mm2;p<0.05]. All asthma endotypes (T2H-A, T2H-nA and T2L) showed significant BM thickening and epithelial shedding despite lack of eos in the T2L. Conclusion: In asthmatic children all endotypes, T2-high atopic, T2-high nonatopic and T2-low, are well represented. The exclusive presence of ILC2 in the T2-high non-atopic asthma, points to this cell as an important driver for this endotype.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".