P98 Neutrophils in lupus: a new phenotype
Why this work is in the frame
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Bibliographic record
Abstract
<h3>Background</h3> Polymorphonuclear neutrophils (PMNs) with irregular properties have been reported in patients with lupus and compelling evidence implicates them as a source of self-antigens. PMNs are the most abundant circulating leukocytes in human blood; defining their implication either as inherently defective players or as cells affected by external factors (e.g. autoantibodies, immune complexes and type I interferon) is of interest. We propose that elements present in the blood of patients with lupus affect neutrophil function/viability, in a NETosis-independent fashion. <h3>Methods</h3> PMNs were isolated from venous blood of healthy volunteers and incubated with serum from normal subjects or from patients with lupus. Apoptosis and necrosis were assessed in real-time by cell surface exposure of phosphatidylserine (PS) and loss of plasma membrane integrity, respectively. Serums’ analytes measurements were made by Luminex and ELISA. <h3>Results</h3> Serums from patients with lupus caused a transient increase in PS exposure on the outer leaflet of PMN plasma membrane, in a significantly more intense fashion than serums from normal individuals. This peculiar phenomenon, which does not have characteristics of classic apoptosis, correlated with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), in contrast to any of the following serum analytes: cytokines, chemokines, circulating growth factors, HMGB1, S100A8 and A9 proteins, complement components C3 and C4, immunoglobulins (IgA, IgG, IgM) and leukocyte counts. However, the transient PS increase was abolished by the decomplementation of the serums or by blocking the Fc receptors on PMNs’ surface. <h3>Conclusions</h3> Healthy PMNs are affected by the serum of patients with lupus. The transient PS exposure on the outer leaflet of the cellular membrane constitutes a new phenotype directly linked with factors that are at play in the blood of patients. Ongoing studies are looking at the nature of this new phenotype and how it links with PMNs being a potential source of self-antigens and/or as players unduly activated in lupus.
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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) | 0.002 | 0.003 |
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 it