A prototypical phenotype for neutrophils in lupus: the potential contribution of immune complexes
Bibliographic record
Abstract
ABSTRACT Purpose Systemic lupus erythematosus is an autoimmune disease hallmarked by a plethora of autoantibodies, interferon-signature, auto-immune complexes, dysregulation of soluble factors in circulation, and abnormal neutrophils. We characterized the neutrophil phenotype in a cohort of lupus patients and assessed the implication of the cells environment. Methods Blood samples were analyzed for neutrophil expression of surface markers and viability, by flow cytometry. Neutrophils from healthy volunteers were stimulated with serum samples from lupus patients. Plasma samples were subjected to multiplex analysis. Whole blood and isolated neutrophils were stimulated with lupus-relevant soluble factors or with heat-aggregated IgGs that mimic the engagement of Fc gamma (Fcγ) receptors by immune complexes, for viability and activation analysis. Results Lupus neutrophils displayed significant alterations in the expression of surface markers of adhesion, complement regulation, degranulation, and immune complex response. They also had reduced viability and increased apoptosis. Stimulation of healthy neutrophils with lupus serum increased apoptosis. Lupus-relevant soluble factors accelerated neutrophil apoptosis. Heat-aggregated IgGs mirrored most of the key alterations in viability and surface marker expression observed in lupus neutrophils. Conclusion This study offers a prototypical phenotype for neutrophils in lupus, characterized by shortened viability, partial degranulation, heightened adhesion capacity, and responsiveness to complement activation. It also points to Fcγ receptors engagement as a major driver of the phenotype observed herein. Finally, results emphasize the therapeutic potential of targeting neutrophil-immune complex interactions and the inflammatory plasma milieu in lupus, from which neutrophil dysfunction is largely acquired. HIGHLIGHTS Neutrophils from patients with lupus exhibit abnormal phenotype and viability. Analysis of plasmas in lupus reveals altered levels of analytes. Stimulation of healthy whole blood with a model of immune complexes reproduces most of the neutrophil phenotypic abnormalities observed in lupus. Neutrophil abnormalities in lupus are largely acquired, rather than representing subsets. GRAPHICAL ABSTRACT
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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 | 0.000 |
| 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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".