Investigating the Role of Complement in Membranous Nephropathy Using a Novel Ex Vivo Podocyte Model
Bibliographic record
Abstract
Background: Membranous nephropathy (MN) is an immune-mediated glomerular disease and is the commonest cause of nephrotic syndrome in adults. Progressive loss of kidney function leading to end-stage kidney disease occurs in up to one third of patients. We aimed to explore the potential functional link between antibody positive primary MN and the innate immune complement system using an ex vivo model of human podocytes. Methods: Using a human podocyte ex vivo model, we evaluated complement activation via immunofluorescence staining for deposition of C3b and C5b-9, and functional alterations (demonstrated by cytoskeletal rearrangement) via IF staining for ActinGreen. Activation of complement via the classical pathway was used as positive control (incubation of podocytes with anti-CD59 and 50% NHS for 30 min), whereas NHS-only treated cells were used as negative control. Four patients with biopsy proven primary membranous nephropathy and detailed clinical phenotype were recruited from the Toronto GN Registry. To determine the role of complement in MN pathogenesis, podocytes were incubated with patient serum for 30 min. Results: 2/4 patients who were nephrotic, antibody (aPLA2R or THSD7A) positive with no current immunosuppression demonstrated (1) positive C3b and C5b-9 staining confirming complement activation (Fig. 1A), and (2) reduced actin staining confirming impaired cytoskeletal organization (Fig. 1B). The remaining 2 patients with negative findings were Ab positive and treated with rituximab at the time of sample collection.Figure 1Conclusions: We successfully applied a new ex vivo model using podocytes to demonstrate complement activation in non-immunosuppressed MN patients. Further studies are needed to elucidate the detailed structural and functional consequences of complement activation in MN.
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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) | 0.001 | 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".