404 The importance of FcγRIIA in antibody-mediated neurovascular thrombosis
Bibliographic record
Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease that damages many organs and tissues. SLE is characterized by the production of autoantibodies and the presence of circulating immune complexes (ICs) in blood. Neuropsychiatric lupus erythematosus (NPSLE) refers to the neurological and psychiatric symptoms directly related to SLE. Alterations in the blood-brain barrier (BBB) and presence of IgG antibodies have been observed in the brain of individuals affected by NPSLE. ICs bind Fcγ receptors (FcγRs), which signaling can play a major role in inflammation and thrombotic events. FcγRIIA receptor is expressed by many immune cells, such as platelets and neutrophils in humans, but it is absent in mice. This explains in part why the interactions of platelets and neutrophils with the brain vasculature endothelium in response to ICs have never been investigated. In this study, we used nanoscale-resolution chip mapping scanning electron microscopy to study the brain vasculature of lupus-prone mice expressing the FcγRIIA transgene (NZB/NZWF1.FcγRIIATGN). We found neutrophils (figure 1A), platelets (figure 1 B-C) and immune complexes (figure 1C) adhered to the endothelium of the brain vasculature. To visualize and quantify at the cellular level the events taking place in the brain vasculature in response to systemic administration of surrogate ICs, we generated Ly6gCre+/-::Rosa26-TdT+/-::CD41-YFP+/- mice expressing the FcγRIIA transgene and fluorescence in neutrophils (red) and platelets (yellow). Using real-time videomicroscopy to capture high velocity events and an unbiased computer assisted analysis approach, we provide images and quantifications of the cellular responses downstream of FcγRIIA stimulation. We observed platelet aggregation and neutrophil adhesion to blood vessel walls in response to ICs, only in FcγRIIATGN mice. Moreover, stable and transient interactions between platelets and neutrophils were captured in real time. Taken together, the results highlight the importance of the FcγRIIA receptor in neutrophil adhesion to the BBB in response to ICs and suggest the potential implication of neutrophils and platelets in mediating alterations of the BBB in NPSLE. This study puts forward an imaging and quantifying approach in a quadruple transgenic mouse model that can be utilized for the study of the pathogenic roles of ICs disease.
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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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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 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".