Tumor necrosis factor α-induced protein 3 (A20) is dysregulated in pediatric Crohn disease
Bibliographic record
Abstract
Purpose: A significant feature of pediatric inflammatory bowel diseases (IBD), which include Crohn disease (CD), and ulcerative colitis (UC), is failure to suppress inflammation. The inability to regulate inflammation renders a major challenge toward establishing effective treatments in IBD. Nuclear factor kappa-light-chain-enhancer of activated B-cells-induced inflammation is inhibited by A20 through interactions with TAX1BP1 (Tax1-binding protein 1) and A20-binding inhibitor of NF-κβ activation (ABIN)-1 (A20 binding and inhibitor of NF-κβ) and upon phosphorylation by inhibitor of nuclear factor kappa-β kinase subunit beta (IKKβ), which stabilizes it. We hypothesized that dysregulation of A20 is an important factor in uncontrolled inflammation in pediatric IBD. Patients and methods: Gene expression of A20 , IKKβ , ABIN-1 , TAX1BP1 , A20 protein, cytokine levels, and A20 phosphorylation was analyzed in the terminal ileum (TI) of 39 patients (14 non-IBD, 15 CD, and 10 UC). A20 expression and protein in T-84 cells and ex vivo biopsies of patients were measured after treatment with Escherichia coli strains or tumor necrosis factor (TNF)-α. Results: TNF-α levels and A20 expression were increased in the TI of CD patients. A20 protein levels and ABIN-1 expression were low, TAX1BP1 expression was high, and IKKβ was unchanged. A20 expression positively correlated with biopsy TNF-α levels and inflammatory markers in CD patients. A20 phosphorylation appeared lower in CD patients. A20 expression in TI biopsies from CD patients and T84 cells was triggered with E. coli , strain LF82, while A20 protein levels remained unchanged. Conclusion: We describe a potential mechanism related to failure of A20 to suppress inflammation in CD, characterized by high A20 expression and low A20 protein levels. The dysregulation of A20 is potentially due to alterations in ABIN-1 , and infection with E. coli strain LF82 could affect the function and stability of A20. Our study signifies an important finding in A20 regulation in IBD, which prevents it from suppressing inflammation. Keywords: A20, ABIN-1, inflammation, NF-κβ, TAX1BP1, E. coli
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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 | 0.000 | 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".