The amphiregulin- epidermal growth factor receptor axis as a therapeutic target in sepsis
Bibliographic record
Abstract
The Epidermal Growth Factor Receptor (EGFR) and its ligand, amphiregulin (AREG) are critical for epithelial cell proliferation but their important role in inflammation and infection is increasingly described. We recently discovered that the EGFR ligand, amphiregulin, could identify a cohort of infants with sepsis, even when CRP was low, identifying it as a potentially adjunctive biomarker for early infection. Its role in adult sepsis however, has yet to be delineated. We conducted a prospective observational study of 42 critically ill septic adult patients on the Intensive Care Unit, comparing serum amphiregulin levels and the frequencies of EGFR-expressing myeloid and lymphoid cells (using spectral flow cytometry) in sepsis survivors and non-survivors, and 20 healthy volunteers. We demonstrate, for the first time, the strong association between serum amphiregulin and in-hospital mortality (AUROC = 0.87). Moreover, we demonstrate that a higher frequency of circulating CD4 + and CD8 + lymphocytes express either the ligand (AREG) or receptor (EGFR) ex vivo, in sepsis, and expression of CD4 + lymphocyte EGFR was associated with several features of immunosuppression. Together, our data suggest that EGFR-signaling represents a novel candidate of T cell dysregulation in sepsis and warrants further investigation.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".