The role of Inositol 1,4,5 triphosphate kinase C in the pathogenesis of Kawasaki disease
Bibliographic record
Abstract
Kawasaki disease (KD) is a childhood multisystemic vasculitis resulting in the development of coronary aneurysms. Functional polymorphism in Inositol 1 , 4 , 5-triphosphate kinase C ( ITPKC ) has recently been identified and linked to KD susceptibility and severity. ITPKC acts as a negative regulator of T-cell activation through the inhibition of Ca /Nuclear factor of activated T-cells (NFAT) signalling pathway. Lactobacillus casei cell wall extract induced coronary arteritis is an animal model of KD dependent on superantigenic activity. To determine the role of ITPKC in the pathogenesis of KD. To assess the role of ITPKC in lymphocyte activation, mouse splenocytes were stimulated with superantigen and T-cell proliferation, cytokines production, Ca flux and ITPKC protein expression were measured by H thymidine, ELISA, flow cytometry, and Western blot, respectively. To confirm the results in a human system, lymphocyte activation was determined in a human cell line after siRNA knockdown. ITPKC was upregulated at both mRNA and protein levels by mouse splenocytes following superantigen stimulation. Cyclosporin A inhibition of Ca /NFAT signalling abolished T-cell proliferation and cytokine production following superantigen activation. ITPKC knockdown in superantigen activated human lymphocyte cell line could not completely inhibit cytokine production or Ca flux. Although ITPKC and the Ca /NFAT signalling pathway were activated in lymphocytes following superantigen stimulation, inhibition of ITPKC was not able to alter lymphocyte activation or Ca flux pointing to overlapping or compensatory pathways. These findings may account for the conflicting reports on the association between ITPKC polymorphisms and KD in different ethnicities.
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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".