Potential Roles of Autoantibodies Targeting the Podocyte in the Idiopathic Nephrotic Syndrome
Bibliographic record
Abstract
Background: The idiopathic nephrotic syndrome (INS) is characterized by heavy proteinuria, hypoalbuminemia, and edema. In both forms of INS, minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), podocytes are injured by mechanisms that are still mostly unknown. This injury causes changes in their actin cytoskeleton, leading to the effacement of their foot processes. Recent evidence suggests that autoantibodies targeting the podocyte might play a role in this process. Our objective is to establish if such autoantibodies are implicated in the pathogenesis of INS and to understand how they contribute to podocyte injury and foot process effacement. Methods: As previously published (Hada and al., J Am Soc Nephrol. 2022;33(11):2008-2025.), INS was induced in C3H/HeN mice by immunization with recombinant Crb2, a transmembrane protein expressed both at the murine and human podocyte's slit diaphragm. Immortalized podocytes expressing mouse Crb2 were incubated with serum from Crb2-immunized and control mice, then stained for phospho-ezrin, the phosphorylated form of ezrin, a protein that links Crb2 to the actin cytoskeleton. Sera from human INS patients in active disease and healthy controls were tested with quantitative ELISA specific for anti-Crb2 and anti-nephrin antibodies. Results: C3H/HeN mice developed significant anti-Crb2 antibody titer and proteinuria 4 weeks after immunization. Podocytes incubated with Crb2-immunized mouse serum showed a significant increase in ezrin phosphorylation compared to podocytes incubated with control mouse serum (average staining intensity per cell of 1370 vs 68, p<0.0001). Among 67 INS patients in active disease, 22 (32%) had a positive anti-Crb2 antibody titer and 6 (9%) had a positive anti-nephrin antibody titer, while no healthy controls had a positive titer of either antibodies. Conclusions: Mice immunized with the podocyte protein Crb2 develop an INS-like disease, and their anti-Crb2 antibodies induce phosphorylation of ezrin, which links Crb2 to the cytoskeleton. Such anti-Crb2 antibodies are also present in human INS patients in active disease, along with anti-nephrin antibodies, indicating that autoantibodies targeting podocyte proteins may contribute to the cytoskeletal changes and podocyte injury seen in INS.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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 | 0.000 |
| 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 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".