Abstract 3216: The Serum of Pexelizumab-Treated ST-Segment Elevation MI Patients Reduces Complement Activation but not Cell Apoptosis
Bibliographic record
Abstract
Objective : Complement (C) activation and apoptosis are involved in the pathophysiology of STEMI. Why C inhibition with Pexelizumab (PEX) in the APEX-AMI failed to reduce mortality in STEMI pts undergoing primary PCI is unclear. We therefore examined C activation and cell apoptosis in the serum of APEX pts in a model of human umbilical vein endothelial cells (HUVEC). Methods : Batch analyses of pre-prepared frozen serum of 45 patients from a single center obtained before initiation of PEX and 24h later before drug discontinuation were performed. An amount of 500 μl serum was added to 2 ml endothelial basal medium in HUVEC culture for 72-hour at 37°C, 5% CO 2 and 95% humidity. C4a, C3a, Bb, and MBL of proximal C, and C5a and sC5b-9, the soluble inactive form of C5b9 from the terminal C, were assessed in supernatants by CBA and ELISA assays. HUVEC-bound C5b-9, the membrane attack complex (MAC), was measured by flowcytometry. Apoptosis was quantified as % of HUVEC with DNA fragmentation after permeabilization and cells positive to annexinV and/or propidium iodide (PI). Analyses were performed blinded to treatment allocation. Results(Table ) : Basal levels of all parameters were similar in PEX (n=24) and placebo (n= 21) groups. Proximal C remained unchanged at 24 hours and unaffected by PEX. C5a, sC5b-9, and MAC all significantly increased at 24 hours in the placebo group, but were strikingly inhibited by PEX. MAC elevation correlated with C4a (r=0.322, p =0.004), C5a (0.468,< 0.0001), sC5b-9 (0.490,< 0.0001), and with apoptotic cell numbers by DNA fragmentation (0.449,<0.0001). Despite this, PEX had no detectable effects on apoptosis. Conclusions : In this cell culture model, the serum of STEMI pts containing PEX almost completely inhibited terminal C while preserving proximal C. Why this did not translate into clinical benefit remains to be elucidated. The absence of effect on apoptosis suggests that C activation in PCI-reperfused STEMI is more a consequence than a cause of apoptosis.
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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) | 0.001 | 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 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".