Abstract WP188: A Damage-Associated Molecular Pattern (DAMP) and Neutrophil Count are Associated with Plasma MMMP-9 Concentration After Acute Ischemic Stroke
Bibliographic record
Abstract
Introduction/Hypothesis: The sterile inflammatory response involves activation of the immune system in the absence of infection following trauma, ischemia, or toxins. Matrix metalloproteinase-9 (MMP-9) is a neuro-inflammatory zinc metalloproteinase implicated in secondary injury after acute ischemic stroke. In order to determine whether MMP-9 was associated with a sterile inflammatory response, we examined the association between circulating MMP-9 and extracellular ATP [a marker of a damage-associated molecular pattern (DAMP)] and acute neutrophil count. Methods: We measured plasma MMP-9 and ATP levels in 338 patients who presented to two institutions with acute ischemic stroke and were enrolled in the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) study. Plasma samples and admission leukocyte subsets were collected at 7.0 ± 3.0 hours and 47.7 ± 7.3 hours from stroke onset. ATP was measured using a liquid chromatography-tandem mass spectrometry metabolomics assay. MMP-9 levels were measured by ELISA using a commercially available assay. Results: 338 acute stroke patients were available for analysis. MMP-9 was associated with plasma ATP on admission (Pearson r = 0.24, P<0.0001) and at 48 hours (Pearson r = 0.21, P = 0.0028). MMP-9 levels were also associated with total leukocyte count on admission (Pearson r=0.32, P<0.0001) and at 48 hours (Pearson r=0.39, P<0.0001). Absolute neutrophil counts were the only leukocyte subsets to be associated with MMP-9 on both admission (Pearson r=0.31, P<0.001) and at 48 hours (Pearson r=0.34, P<0.0001). Conclusions: MMP-9 is associated with markers of the sterile inflammatory response, including circulating plasma ATP levels and absolute neutrophil count. In vitro studies have demonstrated that an initial rise in extracellular ATP is associated with increased neutrophil-mediated MMP-9 release. These findings suggest that ATP may be functioning as a DAMP in response to acute ischemia, and is associated with MMP-9 acutely in patients. This study marks the first clinical cohort to begin to characterize determinants of the sterile inflammatory response in acute ischemic stroke.
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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 | 0.000 | 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) | 0.003 | 0.001 |
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".